Herein, we have synthesized several sulfonamides and tested them for their inhibitory activity against carbonic anhydrases hCA I, hCA II, hCA IX, and hCA XII, respectively. Thereby, biphenyl- and benzylphenyl-substituted sulfonamides showed high selectivity against hCA IX and hCA XII; these enzymes are common targets in the treatment of hypoxic cancers, and noteworthy inhibitory activity was observed for several compounds toward hCA I that might be of interest for future applications to treat cerebral edema. Compound  The development of sulfonamides began as early as 1908  was firsCarbonic anhydrases  are essential for life, as they balance acid and base equilibria in tissues and blood through the conversion of carbon dioxide and water into bicarbonate and protons. The importance of CAs can be seen from their high turn-over numbers , which aThese metalloenzymes play a role in numerous physiological and pathological processes. Two out of the fifteen human CA isoforms, namely, hCA IX and XII, are heavily expressed in hypoxic tumors due to the activation of HIF-1/2 (the transcription factor hypoxia inducible factor). CA XII is moderately present, while CA IX is almost nonexistent in normal tissues. This renders them highly promising prospects for developing innovative anticancer drugs. Thus, HIF-1 is associated with tumorigenesis and other physiological or pathological processes, along with biochemical mechanisms that are responsible for these phenomena. Indeed, in hypoxia and particularly in hypoxic tumors, numerous proteins that are implicated in metabolism, pH regulations, angiogenesis, and immunological response are overexpressed due to the HIF signal cascade, rendering these tumor cells rather distinct from their normal counterparts.However, the application of sulfonamide-based inhibitors acting on all different isoforms of CA may result in severe side effects like paresthesias and others, and especially in patients with pre-existing renal, pulmonary, and hepatic diseases, the most important concerns are acidosis, respiratory failure, and encephalopathy . ConsequSeveral sulfonamides have already been synthesized and extensively investigated for their potential as inhibitors of CAs, as they appear to be very promising agents for the treatment of hypoxic tumors, especially for inhibiting the CA isoforms IX and XII since they are in vivo under the control of HIF-1, the transcription factor hypoxia-inducible factor. In particular, SLC-0111 , a sulfoThus, HIF-1 is associated with tumorigenesis and other physiological or pathological processes, along with biochemical mechanisms that are responsible for these phenomena. Indeed, in hypoxia and particularly in hypoxic tumors, numerous proteins that are implicated in metabolism, pH regulations, angiogenesis, and immunological response are overexpressed due to the HIF signal cascade, rendering these tumor cells rather distinct from their normal counterparts. In response to hypoxia, tumor cells also experience transcriptional reprogramming involving increased expression of hCA IX, which maintains the acid–base balance. An overexpression of CA IX has been demonstrated to be associated with a negative prognosis in multiple cancers.SLC-0111 administration negated the hypoxia-triggered overexpression of CA IX and reduced cell viability, and SLC-0111 also hindered cell migration in a wound healing experiment. In addition, transcriptomic profiles exhibited contrasting responses to SLC-0111 administration between normoxic and hypoxic conditions, despite eliciting upregulation of various tumor suppressor genes in both scenarios.Furthermore, SLC-0111 holds an ureido moiety that is found in several compounds used in a broad variety of biomedical applications. Recently, some ureidobenzenesulfonamides have been reported as efficient inhibitors of carbonic anhydrase II [drase II . The inhdrase II . HoweverAAZ, Furthermore, out of all the organs studied, the mammalian central nervous system (CNS) possesses the greatest number of CA isoforms (at least 9). Isoforms I, VB, VII, VIII, X, XI, XII, and XIV are also found, with hCA II being the most prevalent. Carbonic anhydrase inhibitors have been used therapeutically in a number of brain pathologies because of the broad expression range of CA isoforms in the brain. In epilepsy and idiopathic intracranial hypertension, where acetazolamide AAZ,  is one oConsequently, the treatment of cerebral edema became a subject of scientific interest again, since swelling of the brain is a known side effect of some new drugs , since the presence of a urea functionality in the zinc-binding group is among the most promising trends in the design of CAIs.In this study, we were especially interested in the investigation of benzylphenyl and biphenyl derivates, since previous docking studies indicated high binding affinities, which parallels previous results from the literature .1–15 were obtained in good yields and subjected to screening through stop–flow experiments employing enzymes hCA I, hCVA II, hCA IX, and hCA XII, respectively. Acetazolamide , with 3 being also an excellent inhibitor for hCA IX (Ki = 8.2 nm). A graphic comparison of all compounds is depicted in However, it must be noted that compounds 3 exerted significantly lower Ki values for hCA I (compared with standard AAZ) and proved to be a better inhibitor of hCA IX and hCA XII than AAZ . Compound 3 even showed lower Ki values than AZZ with 8.2 nM against hCA IX and 1 nM against hCA XII. The low Ki values for compounds 2 and 3 also resulted in good selectivity factors of 23 to 122 for compound 2. Compound 3, however, held no pronounced selectivity for hCA IX but high selectivity of 78 and 62 for hCA XII.While the biphenyl motif proved to be a very weak binder to hCA I and hCAII, the phenylbenzyl substituted ureas were good inhibitors of all tested isoenzymes and exhibited extraordinarily low KSLC-0111 (i = 454 nM for hCA XII), which is currently used in clinical studies, was the best inhibitor of this study; compound 3, regarding hCA XII (Ki = 1.0 nM), showed similar ADME profiles ; this makes this compound an interesting candidate for further biological studies. The predicted ADME data for all compounds are compiled in the The compound 8 and 10 became evident, approaching nearly 10-fold . Intriguingly, these compounds displayed minimal scaffolding differences, underscoring the pivotal role of subtle alkyl chain structural variances in dictating their divergent inhibitory activities against the targeted isoform. To unravel the molecular basis of these differences, X-ray diffraction experiments against hCA I were called for in order to obtain an insight into the ligand–protein interactions at the atomic level and focus on the tail interaction that underpinned the observed divergent potencies.As mentioned above, treatment of cerebral edema usually includes the application of a CA inhibitor. It might be assumed that a selective hCA I inhibitor might be beneficial for the therapy of this serious and life-threatening disease. Upon close examination of our results, a striking inhibitory disparity between compounds 8 and hCA I, after the initial rounds of refinement, the calculated Fo-Fc map showed, inside the active site, a clear electron density that was compatible with the sulfonamide moiety . ASAP-MS spectra were taken on an Advion expression CMS-L  with an ASAP/APCI Ion source . IR spectra were recorded on a Perkin-Elmer Spectrum Two , detection with UV absorption). Melting points are uncorrected (Büchi M-565). NMR spectra were recorded using VARIAN spectrometers  at 27 °C  and the corresponding isocyanate (1 eq.) in dry acetonitrile (10 mL) was stirred for 12 h at 23 °C, and the precipitate was filtered off and subsequently washed with acetonitrile, ethanol, and diethyl ether (5 mL each), and dried in vacuo to afford 1 was obtained in 72% yield; Rf = 0.54 ; m.p.: 252–254 °C (lit.: [m/z (%) = 342.1 .Following GP, C (lit.:  254 °C);2 was obtained in 48% yield; Rf = 0.50 ; m.p.: 230–232 °C (lit: [m/z (%) = 382.1 .Following GP, °C (lit:  231 °C);3 was obtained in 45% yield; Rf = 0.59 ; m.p.: 219–221 °C (lit.: [m/z (%) = 382.1 .Following GP, 4 was obtained in 42% yield; Rf = 0.53 ; m.p.: 271–272 °C (lit.: [m/z (%) = 398.2 .Following GP, C (lit.:  270 °C);5 was obtained in 65% yield; Rf = 0.45 ; m.p.: 227–229 °C (lit.: [m/z (%) = 322.4 .Following GP, C (lit.:  229 °C);6 was obtained in 53% yield; Rf = 0.45 ; m.p.: 238–239 °C (lit.: [m/z (%) = 322.1 .Following GP, C (lit.:  238 °C);7 was obtained in 70% yield; Rf = 0.42 ; m.p.: 240–241 °C (lit.: [m/z (%) = 310.3 .Following GP, C (lit.:  240 °C);8 was obtained in 68% yield; Rf = 0.37 ; m.p.: 229–231 °C (lit.: [m/z (%) = 244.0 .Following GP, C (lit.:  232 °C);9 was obtained in 54% yield; Rf: = 0.65 ; m.p.: 221–223 °C (lit.: 223 °C); MS (APCI): m/z (%) = 256.3 .Following GP, 10 was obtained in 68% yield; Rf = 0.43 ; m.p.: 194–196 °C (lit.: [m/z (%) = 272.3 .Following GP, C (lit.:  195 °C);11 was obtained in 71% yield; Rf = 0.49 ; m.p.: 202–203 °C (lit.: [m/z (%) = 300.3 .Following GP, C (lit.:  201 °C);12 was obtained in 51% yield; Rf = 0.71 ; m.p.: 262–264 °C (lit.: [m/z (%) = 320.5 .Following GP, C (lit.:  263 °C);13 was obtained in 91% yield; Rf = 0.35 ; m.p.: 261–263 °C (lit.: [m/z (%) = 364.3 .Following GP, C (lit.:  263 °C);13  in MeOH (10 mL), finely grounded KOH  was added, and the mixture was heated under reflux for 4 h. The precipitate was filtered off, washed with MeOH, and dried to afford 14  as a colorless solid; Rf = 0.10 ; m.p. 310–313 °C (lit.: [m/z (%) = 336.4 .To a suspension of C  as a colorless solid; Rf = 0.40 ; m.p.: 209 °C (lit: [m/z (%) = 418.3 .To a solution of sulfanilamide  in acetonitrile (10 mL), 5-chloro-2-phenoxyphenylisocyanate  was added, and the mixture was stirred at 21 °C for 1 day. The volatiles were removed under reduced pressure, and the residue subjected to column chromatography  to afford v/v) glycerol to the mother liquor solution as cryoprotectant. Data on crystal of the complex were collected using synchrotron radiation at the XRD2 beamline at Elettra Synchrotron  with a wavelength of 1.0 Å and a DECTRIS Pilatus 6M detector. Data were integrated and scaled using the XDS program [Crystal of hCA I was obtained using the hanging drop vapor diffusion method using a 24-well Linbro plate. Then, 2 µL of 10 mg/mL solution of hCA I in Tris-HCl 20 mM pH 9.0 was mixed with 2 µL of a solution of 28–31% PEG4000, 0.2 M sodium acetate, and 0.1 M Tris pH 8.5–9.0 and was equilibrated against the same solution at 296 K. The complex was prepared by soaking the hCA I native crystals in the mother liquor solution containing the inhibitor at a concentration of 10 mM for two days. All crystals were flash-frozen at 100 K using a solution obtained by adding 15%  without solvent molecules and other heteroatoms was used to obtain initial phases using Refmac5 . Then, 5ing COOT . The quaing COOT . Crystaling COOT .i values within the enzyme assay. Notably, the ureidobenzenesulfonamides featuring biphenyl (4) and benzylphenyl (2 and 3) substitutions demonstrated exceptional selectivity toward tumor-associated hCA IX and hCA XII. Compound 3 showed a low Ki for the latter enzyme of 1 nM.In conclusion, the synthesized ureidobenzenesulfonamides exhibited remarkably favorable K


Variational autoencoders (VAEs) are a popular generative model used toapproximate distributions. The encoder part of the VAE is used in amortizedlearning of latent variables, producing a latent representation for datasamples. Recently, VAEs have been used to characterize physical and biologicalsystems. In this case study, we qualitatively examine the amortizationproperties of a VAE used in biological applications. We find that in thisapplication the encoder bears a qualitative resemblance to more traditionalexplicit representation of latent variables.


Validity was carried out by nurses specializing in social communication and nursing professionals, including the Brazilian Sign Language and assessment by nursing students. The Content Validity Index and Cronbach’s alpha above 0.8 were considered for analysis.the videos were entitled “Best practices: bathing newborns in the heated crib” and “Best practices: bathing newborns in the incubator”, lasting seven minutes each, divided into six scenes that demonstrated the approach to parents, environment and material organization, preparing newborns, bathing and after-bath care.the videos will support permanent education processes, academic training and professional training in nursing. Ocular, oral and intimate hygiene are part of this care. For other parts of the body, an interval of 96 hours or more is considered, in order to avoid skin infections, temperature variation and stress. When NB do not fit these criteria, the bath should be performed in the bed. This procedure has been differing in hospital institutions, mainly with regard to intervals and necessary care, such as winding, handling in pairs, heat source turned on, adequate room temperature and shorter execution time.Immersion bath is indicated for those NB who have a GA of over 36 weeks, clinical stability and absence of devices such as peripheral or central venous access, drains, oral and nasotracheal tube and non-invasive ventilation.Bearing in mind the importance of paying greater attention to NB’s care needs, especially in neonatal units and at times of excessive handling, such as bathing, basing nursing care on more robust scientific findings capable of directing the best practices that encourage the safety of this clientele, it becomes necessary to adopt attractive training strategies, with a view to acquiring knowledge and behavioral changes in students and nursing professionals.Despite the lack of irrefutable scientific evidence regarding the effectiveness of using pedagogical videos for teaching and learning in nursing, especially in the context of neonatal care, this technology has been indicated for the development of clinical skills and increased self-confidence and self-efficacy, given its contemporaneity, practicality and ability to motivate learners, 7. Also, it strives to minimize aggravating situations for safety, such as exposure to cold, stress, excessive handling and preservation of devices.It is also believed that the educational video is capable of improving the understanding of the care provided by nursing and aligning the assistance provided in this context, from academic training to work practice, with facilitated access, nowadays, via cell phone, which allows the deliberate visualization of procedures before experiencing a simulation or real care practiceGiven the importance of the theme and the absence of studies that produced audiovisual learning objects, based on the best evidence for bathing the NB’s bed in an intensive care unit, the questions arose: Are the educational videos about bathing NB in bed valid in terms of content and appearance to be used as an educational health technology for nursing staff professionals and nursing students? Is the inclusion of Brazilian Sign Language (LIBRAS) in educational videos in line with current regulations?To develop and analyze evidence of content validity of educational videos about bathing NB in bed in a neonatal unit.Universidade Federal do Triângulo Mineiro, whose opinion is attached to this submission. The online Informed Consent Form was obtained from all individuals involved in the study.The study was conducted in accordance with national and international ethics guidelines, and was approved by the Research Ethics Committee of the , visualized in This is applied research and methodological production and technological validity, guided by the framework of quality improvement studies-SQUIRE of the EQUATOR network, developed from December 2020 to February 2022 in three phases, pre-production, production and post-production, adapted and verified through the Brazilian National Council for Scientific and Technological Development  platform, considering up: master’s degree in nursing (4 points); master’s degree in nursing with dissertation in the area of interest of the study (1 point); doctoral thesis in the study area (2 points); clinical experience of at least one year in the area of interest (1 point); certificate of clinical practice  in the area of interest of the study (2 points); publication relevant to the area of interest (2 points); and publication of an article on the subject in a reference journal (2 points). For nurses to be selected, they must obtain a minimum of five points, among those who had a PhD.Participants in script and storyboard validity were 16 PhD nurses, selected according to the inclusion criteria proposed by Fering (1987)Sixteen PhD nursing from the first stage, three specialists in the area of social communication and 43 nursing team members as well as 23 nursing students as evaluators, participated in the validity of the edited video.To be selected as specialists in social communication, professionals should have a degree in social communication, experience with technical support, programming or networking and experience with video editing. To be selected as members of nursing team, they should be working in the maternal and child area for more than five years..For nursing students to be selected as evaluators, they should be enrolled in a higher education nursing course and have taken courses with content on pediatric nursing, gynecology and obstetrics nursing, and women’s, adolescent, and child health nursing. Selection and recruitment were carried out using the snowball technique, which consisted of nominating participants by themselves successivelyLIBRAS validity was performed by three specialists in LIBRAS, selected and recruited through the snowball technique, according to the criteria: acting as a LIBRAS professor or being an interpreter in LIBRAS for more than two years.For a better description and understanding of the development process of the proposed pedagogical tools, in the first phase, pre-production, an integrative literature review was carried out a priori to list the stages of NB bed bath to be included in the script, including the following sources of information: Medical Literature Analysis and Retrieval System Online (MEDLINE), through the US National Library of Medicine National Institutes of Health (PubMed) search engine; Latin American and Caribbean Literature in Health Sciences (LILACS), through the Virtual Health Library (VHL); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Web of Science.Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH)  were used. associated by the Boolean AND operator and their respective synonyms by the OR operator. The strategy was standardized in MEDLINE/PubMed, and reproduced in other data sources according to the specific criteria of each one: “Infant, Newborn”[Mesh] OR  OR (Newborn Infant) OR (Newborn Infants) OR (Newborns) OR (Newborn) OR (Neonate) OR (Neonates)) AND  OR  OR (Newborn Intensive Care Units (NICU)) OR  OR  OR  OR (Newborn ICUs) OR (Newborn Intensive Care Units) OR  OR  OR  OR . A total of 15 studies published between 2015 and 2022 were included, which addressed care with bathing NB in bed. Data were exported to an Excel® spreadsheet and refined for the construction of script scenes/steps’ content.The scripts of the two videos, constructed from bibliographic survey, considered six scenes to present the technique of bathing NB’s bed in a neonatal unit, namely: 1 - Approaching parents and/or family members; 2 - Environment and material organization; 3 - Preparing newborns; 4 - Bath; 5 - After-bath care; and 6 - Environment and nursing note organization. The storyboard for recording described, through freehand drawings made by the main researcher, the filming plans, and the plan for editing covered the texts, formatting, narration and background music.After preparing the first versions of the script and storyboard, the content validity process began with specialists in the second phase and video recording: production. Participants were contacted via email, and at each stage of the validity process, an instrument was developed in HyperText Markup Language (HTML) on Google Forms, filled out via the web, in three parts: participant personal and professional identification; script, storyboard or edited video; and general analysis based on the mentioned instruments. The response option for the items was a Likert scale with five weights ..After recording, LIBRAS was included by an interpreter hired by the researchers, following the mandatory elements, in accordance with ABNT NBR 15290 normsThe scenario in the videos simulated Neonatal Intensive Care Unit (NICU) beds: one with an incubator and another heated crib, including a bedside table, multiparameter monitor and armchair. Before the official recording, rehearsals were carried out to go over the script’s and storyboard’s content with those involved and to verify the equipment and actor positioning. Adjustments were made to achieve the technique’s good quality, in addition to features such as 4K resolution and shot variations  for the same scene. The audio was recorded in a studio with acoustic insulation by one of the researchers. The recording equipment was two Sony A6500 cameras with 35 mm, 70-200 mm and 16 mm lenses, video tripod, led light and H6 zoom recorder with lapel.After recording, the scenes were edited in the post-production phase. The editing program was Final Cut Pro X, and the creation of the intro animation and inclusion of moving texts was Adobe After Effects®. Recording and editing were conducted by the researchers followed by professionals with experience in neonatology and audiovisual technicians. The soundtrack that composed the video along with the narration was the instrumental “carefree” by public domain artist Kevin MacLeod. Then, the edited video was subjected to validity and appearance assessment by specialists and nursing students..Data were stored in a database in Excel® format extracted from Google forms. Then, they were imported into the Statistical Package for the Social Sciences (SPSS) program version 21.0, submitted to descriptive statistics for frequency and percentage analysis, position measurements (mean and median) and variability (standard deviation). Agreement among judges was analyzed using the Content Validity Index (CVI), considering the weights “totally agree” and “agree”, grouped as agreement, and “completely disagree” and “disagree”, grouped as disagreement. The formula used in the calculation was: CVI = agreement/total responses, with items with agreement above 0.80 being valid. In the analysis of nursing students’ assessment, in addition to descriptive statistics, the Wilcoxon test was applied, with a 95% Confidence Interval for the proportion of maximum scores  using a binomial distribution. “Strongly disagree” was the minimum score (1 point), and “strongly agree” was the highest score (5 points). Suggestions for adjustments were incorporated and the instrument was forwarded to PhD nurses for further analysis, following the Delphi technique precepts.Script, storyboard, and edited video reliability was analyzed by Cronbach’s alpha, which checks the internal consistency of a single multi-item construct. Values above 0.80 were considered of high reliability and “Good practices: bathing newborns in the incubator”, lasting seven minutes each. The videos covered nursing interventions and specific care from preparation to bathing, such as donning, checking water temperature with a thermometer, proper management of NB, winding up, handling in pairs and encouraging the participation of a family member: the mother.Two videos were developed that represented a bed bath in the neonatal unit, lasting seven minutes each, “Good practices: bathing newborns in the heated crib”The video “Good practices: bathing newborns in the heated crib” hypothetically presents a preterm NB, 35 weeks old, male, 11 days old, current weight 2,100 g, using an orogastric tube and a central catheter inserted peripherally in the limb top right. The video “Good practices: bathing newborns in the incubator” presents a preterm NB, 31 weeks old, female, 20 days old, current weight 1,400 g, using an orogastric tube, both with indication of bed bath by GA. Emphasis was placed on protecting the venous device with transparent plastic film and encouraging the post-bath kangaroo position for better thermal regulation.The final version of the videos after editing included introduction with title, institution and funding body logos, nine nursing interventions, the six scenes and the credits .In terms of validity, among the 16 PhD nurse judges, 15 (93.7%) were female and one (6.3%) was male. In addition, 11 (68.7%) were from the state of Minas Gerais, two (12.4%) from São Paulo, one (6.3%) from Sergipe, one (6.3%) from Maranhão and one (6.3%) from Santa Catarina. Of these, ten (63.4%) worked in an undergraduate nursing course, three (18%) in Maternal and Child Units, two (12.4%) in teaching and research at a teaching hospital and one (6.2%) in a technical nursing course. Training time ranged from six to 35 years, with an average of 16.3 years.The three specialists in social communication were male and from the state of Minas Gerais. Two (66.6%) worked with video recording and editing in an educational institution and one (33.4%) was a professor with a PhD.Of the 43 nursing team members, all were female and from the state of Minas Gerais. In addition, 33 (76.7%) were nurses and ten (23.3%) were nursing technicians. All working in Maternal and Child Units, 30 (69.7%) in rooming-in and 13 (30.3%) in intensive care. Working time ranged from five to 20 years, with an average of 11.4 years.The three specialists in LIBRAS were female and from the state of Minas Gerais. Furthermore, two (66.6%) worked with video recording and editing in an educational institution and one (33.4%) was a professor with a PhD.In video assessment, carried out with 23 nursing students, 22 (95.7%) of them were female, with an average age of 24 years, minimum of 22 and maximum of 31 years. All were studying nursing at a public institution and, of these, 16 were in the tenth period, four in the new, one in the eighth and two in the seventh.In the first round of script and storyboard content and appearance validity by PhD nurses, the indices were above 0.93 supporting the inclusion of all items for agreement and reliability, with minor reformulations according to the suggestions. These were: include parents in the scene for a humanized assistance, complete donning, not throw water directly on the NB’s skin because it is a great stimulus and change the bed after bathing NB when skin-to-skin contact is not possible. The suggestions were accepted and, after modifications, the script and storyboard were forwarded to PhD nurses for a second round, with no new suggestions. The assessed items indicated that the script and storyboard presented coherent objectives, clear content for understanding the theme with relevance to care practice, and environment and language appropriate to the context and target audience. The CVI and Cronbach’s alpha of the first and second rounds of this stage are presented in The indices of the first round of validity of video appearance by PhD nurses were above 0.98, attesting to the agreement and reliability of the included scenes. Relevant suggestions have been incorporated to improve audience understanding, such as adjusting text time to facilitate reading, inserting the list of necessary materials and sentence “change gloves to perform oral hygiene”.After editing, the video was forwarded to PhD nurses for a second round. There were no new suggestions and the second version was sent to social communication specialists, specialist nurses and nursing students without further consideration. The assessment indicated that the video is configured as a teaching-learning tool about NB bed bath, easy to use, with adequate duration for the number of scenes, good lighting and clear narration. The CVI and Cronbach’s alpha of the rounds in this stage are shown in The indices of LIBRAS validity items were above the recommended level (CVI=1.00), indicating that language was adequate to content and recommended norms. The items assessed by the three specialists in LIBRAS were: LIBRAS agrees with the audio narration; the interpreter is properly positioned on the screen; the interpreter window is well positioned and in focus; and it is possible to identify all the interpreter’s movements and gestures.After the validity stage with specialists, the edited video was assessed by 23 nursing students using the same criteria in a single round. All domains had a mean score equal to 4.86±0.45 with a minimum of 3 and a maximum of 5 points, standard error of 0.95, median of 5.00 and p<0.001, indicating that the video was well assessed by students., 3.Knowing that routine bathing in a neonatal care unit can cause changes in NB clinical stability due to excessive manipulation, exposure to low temperatures, variation in oxygen saturation and other factors, capable of negatively interfering with the safety of these highly vulnerable patients, it is important to invest in innovative teaching objects and tools that are attractive for nursing learning in this scenario. Handling in pairs provides better postural organization for NB, because, while one professional performs care, the other maintains the alignment and containment of arms and legs, reducing stress due to agitation, excessive handling and procedure time. In this context, specific care was included in the video, such as a firm touch with the hands still on NB’s chest to lower the level of the incubator or heated crib and changing the diaper with NB on its side. The winding of NB observed in the video has a positive effect on the vital parameters mentioned, on crying time and on the level of stress, pain and agitation, and is indicated in any type of bath.In the video produced, the bath is performed by two people with cotton soaked in warm water and with the participation of mothers. For a premature baby, touch can be a harmful stimulus, so water should not be directly thrown on the NB’s skin, 19. Physical contact with the NB through touch and the kangaroo position and being able to be present and participate in care, even while observing, provide feelings of closeness and trust and strengthen the bond among family members. Commitment to care contributes to the development of parenting during hospitalization, breaking down the barriers generated by the NICU’s complex and technological environment. Thus, nurses should encourage the presence and participation of family members in care.In the daily life of a NICU, family members present must be included in NB care to build a bond whenever possible.A study that developed and assessed an educational video on relief of acute pain in babies pointed out that the presence of family contributes to NB development and construction of bonds and affection among members and that using videos before procedures can bring them closer to content.The video developed in this study contemplates these precautions and visually demonstrates how to do them. This tool facilitates the teaching-learning process and contributes to acquisition of knowledge, as long as the methodological paths for its elaboration are respected, as a survey of the best scientific evidence on a given care and validity process by specialists, which allows assessing whether content is adequate for what is intended. In this regard, nursing has engaged in the production and validity of educational videos on various topics to be applied during continuing education, training and professional training actions. Scene duration and dynamics influence the interest of those who watch long videos longer than eight to 12 minutes, dispersing attention. Therefore, the videos developed in this study fit the recommendation.To instigate viewers, the video must be dynamic, have attractive images consistent with reality and be short in duration. Realism provokes feelings and emotions, and brings it closer to everyday practice, and the step-by-step details contribute to the development of skill. Incorporating videos into the teaching practices of students and professionals makes it possible to explore various low and high complexity topics and disseminate them on free online platforms that maximize reach without territorial limits.In the video developed in this study, the scenes were filmed in several planes to attract attention, and the scenes were viewed from above convey the feeling of bathing, bringing viewers closer to the scene. A study that assessed videos for clinical teaching pointed out that quality influences viewers’ understanding.The inclusion of LIBRAS is a differential resource in the video, which allows accessibility for teaching the deaf. This is a limitation cited by other studies. It may improve communication among professionals and deaf parents/relatives about this procedure. It is difficult to find health professionals and professors trained to work with this public in teaching and care practice, creating barriers in the transmission of knowledge, which is why audiovisual technologies with translations can facilitateThe videos developed are presented as contemporary learning tools, subsidizing neonatal safety with standardization of the technique that includes specific care to prevent hypothermia, reduce stress and excessive handling and encourage the presence and participation of parents. In nursing, they will be able to mediate students’ and professionals’ teaching-learning process. As they are attractive and dynamic, arouse the interest of those who watch them, favoring actions. We highlight the inclusion of LIBRAS to expand content accessibility. Also, by presenting the material and human resources necessary for a safe, scientifically based bath, the videos can help managers in planning available and necessary resources for actually providing assistance based on scientific evidence.The limitation of this study can be attributed to the representation of a specific culture of technique and humanization in care regarding bathing in a neonatal unit, which may differ in other countries. Moreover, the material and human resources presented in the videos may be restricted in some units.This study allowed the development and validity of educational videos about the NB bath in bed in neonatal units by PhD nurses specialist in social communication, nursing staff and nursing students. Two videos were developed that could contribute to academic training, permanent education and professional training in the field of neonatology. The scenes were divided into six precautions and LIBRAS was included, and all items assessed had CVI and Cronbach’s alpha above 0.90. It is recommended that future research be carried out to assess the effectiveness and applicability of the video during these training activities.The videos can be watched online and contribute to health education processes about bathing NB in a neonatal unit and the path to development can provide subsidies for the creation of new videos. Therefore, videos’ ability to translate scientific evidence into practice in an applicable, playful and accessible way can create means for the translation of scientific knowledge with potential for the real improvement of nursing care practice.


The flexibility of insect wings should be considered in the design of bionic micro flapping-wing aircraft. The honeybee is an ideal biomimetic object because its wings are small and possess a concise vein pattern. In this paper, we focus on resilin, an important flexible factor in honeybees’ forewings. Both resilin joints and resilin stripes are considered in the finite element model, and their mechanical behaviors are studied comprehensively. Resilin was found to increase the static deflections in chordwise and spanwise directions by 1.4 times and 1.9 times, respectively. In modal analysis, natural frequencies of the first bending and first torsional modes were found to be decreased significantly—especially the latter, which was reduced from 500 Hz to 217 Hz—in terms of resilin joints and stripes, closely approaching flapping frequency. As a result, the rotational angle amplitude in dynamic responses is remarkable, with an amplification ratio of about six. It was also found that resilin joints and stripes together lead to well-cambered sections and improve the stress concentrations in dynamic deformation. As resilin is widespread in insect wings, the study could help our understanding of the flexible mechanism of wing structure and inspire the development of flexible airfoils. The flight of insects has attracted much attention in many fields, especially that of insect-mimicking flapping-wing micro air vehicles (FMAVs). FMAVs refers to aircraft that can fly at low speed and at various altitudes, like birds and insects, and achieve hovering, forward, and backward flight with high maneuverability and low power consumption . The sizExperiments have shown that there are obvious deformations, including twisting and bending, in the wings of insects such as dragonflies, butterflies, and bees during flight ,3. ThrouPrevious researches found that resilin—generally, the resilin-bearing vein joints—was found to contribute a lot to the chordwise flexibility of the wings of insects such as dragonflies, beetles, and bumblebees ,7,8,9,10In addition to the general resilin-bearing vein joints, there are resilin stripes in areas where the longitudinal vein and membrane are connected in some insect wings. Ma et al.  found coHoneybees are small and excellent at hovering. Their maximal wingspan is about 1 cm. The wings of a honeybee include forewings and hindwings, and the latter are much smaller. In this paper, the forewing is considered in analysis. The wing base is quite narrow and connected with the thorax muscle and it is supported mainly by the robust longitudinal veins in front, namely, the costa, cubitus, and anal veins. Compared with insects such as dragonflies, honeybees have more concise vein venation and much fewer vein joints. Veins in the central area are radius and media veins, which form several joints and cells with irregular shapes. The posterior edge is soft and not completely wrapped by veins. The wing surface is relatively flat, and the small vein corrugations were not considered in the model for lack of precise measurements. As shown in The finite element model was built from a photo of a honeybee forewing in the ABAQUS software, as shown in The huge difference in material properties between resilin and chitin was brought into focus. Young’s modulus of vein and membrane constituted by chitin are 4.8 GPa and 2.8 GPa, which is thousands of times higher than that of resilin (0.1–3 MPa). Therefore, the area connected by resilin is considered to be very soft and flexible compared with other areas. This justifies the following simplifications in the finite element model. Firstly, the resilin joints were built by setting the vein junctions as hinged. Secondly, the resilin stripes were simulated by allowing the relative rotation of the nodes in vein-membrane adjacent elements. By using these approaches, the flexible effects of resilin are fully considered in the models. Details such as the unsymmetrical distribution of resilin in dorsal and ventral sides were not taken into account in the modeling.X-axis and Y-axis, as shown in The wings of honeybees always flap at high frequencies in flight, and the main loads are borne by inertia and aerodynamic force. The higher frequency the wing flaps, the more significant effects the inertia produces. Flapping motion is similar to fixed-axis rotation, and the constraints and motions are all applied on the wing base in the following analysis. Due to the structure flexibility and inertial force produced in dynamic flapping under the given motion, deformation of the wing can be observed. According to previous researches ,25,26, tIn order to illustrate the roles of resilin joints and stripes comparatively, four models were built, as follows: model 1 without resilin, model 2 with resilin joints, model 3 with resilin stripes, and model 4 with both of resilin stripes and resilin joints. The mechanical behaviors of the four models are studied and compared, using both static and dynamic analyses, in the following section.−5 N is applied at about 85% of chord length in the trailing edge. An experimental method to measure the chordwise stiffness of bumblebee wing was proposed by Mountcastle and Combes ,13. By fBoth resilin joints and stripes have significant effects on wing flexibility from the comparisons of The contours of displacement and stress of the models are shown in Furthermore, this shows that the stress also concentrates near the end of anal vein, where the streamlined edge is curved. In fact, the forewing and hindwing are linked here by coiled membrane and a hook structure, achieving synchronous movement for honeybees. This special structure works with resilin to eliminate stress concentration, avoiding structural failure in flapping cycles ,28.The natural frequency is associated with the mass and stiffness of the wing. To understand the global stiffness of the models, modal analysis was carried out on the section. The total mass of the wing model was calculated as 130 mg, close to the experimental measurement of 102 mg . With thThe vibration modes of model 1 and model 3 are exactly the same, namely, the first-order bending mode, second-order bending mode, and first-order torsional mode. They differ only in that the frequencies of model 3 were lowered by 20–30% as resilin stripes were introduced. The first three vibration modes of model 2 and model 4 are first-order bending mode, second-order bending mode, and first-order torsional mode, which are different from that of model 1 and model 3. The most obvious difference is the frequency of the torsional mode, which was reduced from 500 Hz in model 1 to 239 Hz in model 2 and to 217 Hz in model 4. The results indicate that resilin joints have the most significant influences on rotational stiffness of a wing with a fixed base. The first bending frequency was decreased by about 20% in model 3, and by 40% in model 2 and model 4. As for the second-order bending mode, its frequency was least changed among the four models.As flapping movement is driven by the basal muscles, flexibility and deformation will always influence the dynamic responses under the given basal motion. Hence, dynamic responses are simulated in this section to further study the roles of resilin. The flapping and rotational angles in Equation (1) are applied at the wing base, and the initial amplitudes are The analysis time is 0.05 s, about 10 flapping periods. The frequency of the excitation is 197 Hz, falling in between the natural frequencies of the first-order bending mode and second-order bending mode for model 1 and model 3 and between the first-order bending mode and first-order torsional mode for model 2 and model 4. The base vibration mode is bending for all the four models. Therefore, the flapping angles shown in The simulation shows that the six resilin joints increase the deflection in chordwise and spanwise directions by 74% and 183%, respectively. The chordwise stiffness of bumblebee forewing was found to be increased by more than 30% when one resilin-bearing joint located in the center was fixed artificially in the experiment . To compAs vein corrugations have little effects on the chordwise stiffness, the simulation is basically consistent with experiment, though the small vein corrugations are not considered in the finite element models. The small differences between experiment and simulation occur because the diameter of the vein splint used in the experiment was 0.4 mm, which is much larger than the size of resilin joints in the finite element model. As for spanwise flexibility, the effects of resilin on deflection should be reconsidered when the pattern of vein corrugation which contributes to spanwise stiffness is introduced in the model. After all, the bending deformation of insect wings is restrained in flapping by the rigid and corrugated longitudinal veins. In aerodynamics, excessive spanwise bending can lower effective angles of attack and, consequently, lower aerodynamic force generation . In addiIn previous studies, it was found that the cambered sections of deformed wings of dragonflies and honeybees are related to resilin joints ,31. ThisDriven by the basal muscle, insect wings are flapped at frequencies of tens to hundreds of times per second during flight. The input excitation from muscles is transmitted through the wing structure to produce the flapping motions. To satisfy the demands of aerodynamics, the flapping motion should always meet a certain amplitude and frequency to provide enough lift and thrust. It must be a formidable challenge for insects with only wing base connected with muscles if the wing is fully rigid. As the flexibility contributing factors, there is no doubt that the resilin joint and stripe will play roles in this dynamic process. Modal analysis shows that the natural frequency of the first torsional mode is dramatically reduced, by more than 50%, and more closely approaches the given frequency when resilin is introduced, especially resilin joints. This leads to a remarkable increase in rotational angle amplitude in dynamic responses.To study the flexible roles of nodus in the flapping efficiency of dragonfly wings, the amplification ratio was defined as the ratio of displacements of the wing tip and wing base in a vibration test . The samresponse . The magThe insect wing plays a very important part in transmitting motion and force during flapping and deformation. In this research, resilin joints and stripes, which have received much attention in recent years, are considered in the honeybee forewing by the finite element method. Their roles in determining overall wing stiffness and shaping wing deformations during flight are studied through both static and dynamic analysis. In static analysis, the six resilin joints have similar effects on chordwise flexibility to that of resilin stripes. Spanwise flexibility, by contrast, is influenced much more greatly by the six joints. Meanwhile, it was found that resilin stripes produce exactly the same effects on the two stiffnesses. In modal and dynamic analysis, resilin stripes result in a reduction of about 20–30% in each natural frequency, while resilin joints make a significant contribution, of up to 50%, to the reduction of torsional frequency. In dynamic analysis, together, they lead to the amplification of the amplitude of the dynamic rotational angle under base velocity by six times. Meanwhile, the wing sections are well cambered to benefit aerodynamics. This means that certain torsional angles and section shapes could be induced passively with resilin, due its effect on wing flexibility, to meet aerodynamic demands. In addition, it was found that the stress concentrating at the junction areas is improved when both forms of resilin are used in the models.The results in the paper are based on the analysis of the finite element model of the honeybee forewing, with some simplifications. Although the actual irregular patterns of resilin on the wing are ignored, it is the first time that a study comprehensively considers the effects of both resilin joints and resilin stripes, and some meaningful conclusions are obtained. To obtain more accurate dynamic response behaviors of insect wings, the following improvements should be considered in future work. Firstly, the full coupling relationship of wing structure elasticity, inertia, and aerodynamics should be considered comprehensively. Secondly, the finite element model should be more accurate to be closer to the real wing. For example, the asymmetry of resilin in dorsal and ventral sides is well worth considering.


The 21st century has seen wide‐ranging changes in drinking locations in Great Britain, with on‐trade alcohol sales decreasing and off‐trade sales increasing. To better understand the underlying time‐trends in consumer behaviour, we examine age‐period‐cohort (APC) effects related to changes in the share of individuals' drinking occasions taking place in: (i) on‐trade versus off‐trade locations; and (ii) specific on‐trade or off‐trade locations, that is traditional/community pubs, modern pubs/bars/café bars, nightclubs/late‐night venues, restaurants/pub restaurants, social/working men's clubs, golf/other sports clubs/venues, at home  and at home .N = 162,296 men, 138,452 women).Repeat cross‐sectional 1‐week drinking diary data, collected 2001–2019. APC analysis via negative binomial regression models for each gender (A smaller/declining proportion of occasions took place in on‐trade compared to off‐trade locations. Recent cohorts tended to have a larger share of on‐trade occasions than previous cohorts, driven by their larger share of occasions in modern pubs/bars/café bars and nightclubs/late‐night venues. Meanwhile, occasions in social/working men's clubs, golf/other sports clubs/venues and traditional/community pubs tended to be popular among older men, but have declined. Finally, the growth of off‐trade drinking appears to be driven by a growth of off‐trade drinking in non‐social settings, in particular by older people/cohorts.Our findings highlight the declining prominence of certain on‐trade locations, and increasing prominence of home drinking in non‐social settings, within British drinking practices. While rising non‐social home drinking is concerning, it is positive from a public health perspective that it does not appear to be shared by recent cohorts. Total per‐capita consumption rose to a historic peak in 2004, before subsequently declining steeply , 4, 5, bRecent decades have also seen changes in how people distribute their drinking across different locations. Sales data suggests that on‐trade sales  have decreased, while off‐trade sales  have increased . SimilarThe drivers of this on‐trade to off‐trade shift are currently not fully understood. One potential explanation relates to affordability. It has been noted that cheaper competition from supermarkets encourages people to increase the share of their consumption occurring at home . MeanwhiA popular method for examining alcohol‐related trends is age‐period‐cohort (APC) analysis. The goal of APC analysis is to support understanding of changes in a given outcome of interest over time, with the rationale being that such changes can be attributed to three distinct processes: (i) ‘age effects’, that is, variations associated with chronological age; (ii) period effects, that is, variations over time periods or calendar years influencing all age‐groups simultaneously; and (iii) cohort effects, that is, changes across groups of individuals born in the same year or years , 24.UK‐based APC studies on alcohol tend to suggest strong age and cohort effects. For example, one study suggests that rising alcohol consumption from 1994 to 2004 was linked to older lower‐consuming cohorts being replaced in the population by more recent higher‐consuming cohorts, while more recent declines in consumption are linked to increased abstinence among recent cohorts . Other UHow does the share of men's and women's drinking occasions taking place in on‐trade and off‐trade locations differ by age, period and cohort?How does the share of men's and women's drinking occasions taking place in specific on‐trade and off‐trade locations differ by age, period and cohort?While the above studies focus on alcohol consumption/harm, there are currently no known APC studies focussing on drinking locations, as few long‐running data series provide information on this. We address this by making use of repeat cross‐section market research data collected by market research company Kantar to conduct an APC analysis on changes in drinking occasion locations in Great Britain (2001–2019). Men and women are analysed separately as previous research highlights gender differences in: (i) location/beverage preferences  ; and (ii22.1https://osf.io/tvrw2/).APC analysis of repeat cross‐sectional market research data from Kantar Alcovision (2001–2019). Our analysis plan was pre‐registered using the Open Science Framework . Previously, from 2001 to 2008, Alcovision used on‐street sampling with the same quota‐based approach . To deal with potential representativeness issues due to the use of quota sampling, we compute sampling weights using a ‘raking’ technique that adjusts the marginal distribution of the target variables to align with UK census data  were excluded from the analysis. Birth cohorts from before 1930 (N = 3175) and after 1999 (N = 2862) were also excluded from the main analysis due to their small sample sizes and only being observed at very young or old ages.Alcovision's annual sample size in our analysis period was approximately 12,500 under on‐street sampling (2001–2008) and approximately 20,000 under online sampling (2009–2019). Our final analytical sample across the entire 2001–2019 analysis period was 300,748 adult drinkers in England, Scotland or Wales. Alcohol abstainers  [2.3.2We use Alcovision's drinking diary component to create outcomes measuring the individual‐level share (%) of drinking occasions occurring in various locations. First, the share of individuals' occasions taking place in: (i) on‐trade locations; and (ii) off‐trade locations is measured. Second, the share of individuals' occasions taking place in the following specific on‐trade and off‐trade locations is measured: (i) traditional/community pub; (ii) modern pub/bar/café bar; (iii) nightclub/late‐night venue; (iv) restaurant/pub restaurant; (v) social/working men's club; (vi) golf/other sports club/venue; (vii) at home ; and (viii) at home . These are defined as the share (%) of each respondent's occasions which include drinking in each location. The ‘at home’ measures include occasions in own homes, holiday homes or someone else's home. They are separated into social or non‐social settings by using additional information on the reported purpose of the occasion. ‘Social setting’ includes occasions reported as ‘sociable night in/catch‐up/planned sociable occasion’, ‘a big night in/party/special occasion’, ‘a barbeque/picnic’ or ‘friends/family unplanned occasion/having friends round’. ‘Non‐social setting’ includes occasions reported as ‘regular evening/lunchtime/everyday drink’, ‘rounding off the evening’ or ‘just having a drink/drink after work/quiet night in’. Occasions taking place in student pubs/union bars, hotels, cinemas/theatres, bowling/bingo/leisure venues, outdoors, at festivals/events or in unknown/unlisted venues were all excluded from the specific locations analysis due to low prevalence .2.4First, APC trends are analysed via descriptive analysis, whereby the weighted mean of each outcome is plotted by gender and APC variables. Second, APC effects are formally modelled for each outcome using negative binomial regression models. Negative binomial regression is a commonly used method within APC studies in alcohol literature , 25, 27,In each model, APC measures are included as explanatory variables, with the 35–49 age‐group, 2009 period and 1960s cohort being reference categories. To account for the aforementioned switch from on‐street to online data collection between 2008 and 2009 a binary control variable is also included in each model . To remove perfect collinearity between the period measure and the binary control for the change in data collection, 2008 is omitted as a category from the period measure .Cohort effects suggest that, in general, the share of occasions in the on‐trade was higher among more recent cohorts.3.2.2The share of occasions in traditional/community pubs tended to decrease with age for women . The share of occasions in modern pubs/bars/café bars was fairly stable throughout the analysis period, while there was a small decrease in the share of occasions in nightclubs/late‐night venues. There was no clear pattern in period effects relating to restaurants/pub restaurants, which tended to fluctuate up and down every few years. Meanwhile, there was a consistent decline in the share of occasions in social/working men's clubs, and this was statistically significant among men . Following a rise in the 2000s, there was also a statistically significant and consistent decline in the share of men's occasions in golf/other sports clubs/venues in the 2010s. Finally, the share of occasions at home  was fairly stable during 2001 to 2011 but subsequently declined slightly, while the share of at‐home  occasions increased consistently.Cohort effects suggest the share of occasions in traditional/community pubs was highest among the 1950s–1960s cohorts, whereas the share of occasions in modern pubs/bars/café bars and in nightclubs/late‐night venues was highest among recent cohorts. Meanwhile, the share of occasions in restaurants/pub restaurants was highest among pre‐1960s cohorts and the 1990s cohort, while the share of occasions in social/working men's clubs and in golf/other sports clubs/venues was highest among older cohorts. Finally, the share of occasions at home  was highest among recent cohorts, and at home  highest among older cohorts.3.3An overall summary of the findings from all of the above analyses is provided in Table 3.4The results of the two sensitivity analyses are provided in 4The study is the first known APC analysis of drinking locations. The results provide novel insights into changes in the distribution of British drinking occasions across the on‐trade and off‐trade, and across specific on‐trade and off‐trade locations.First, our findings highlight that a smaller, and declining, the proportion of drinking occurs in the on‐trade than the off‐trade. This is in line with existing analysis of sales data  and withWhile the on‐trade generally remains a young person's place, certain on‐trade settings  have tended to be more popular among older men. The share of occasions in these locations has declined throughout (at least parts of) the 21st century. This suggests that the shift away from on‐trade drinking in recent decades is likely to be linked to reduced drinking in these specific locations, while the share of occasions in locations like modern pubs/bars/café bars which are popular among young people have remained fairly constant.Importantly, our findings suggest that the on‐trade locations that in the past have had the greatest gender differences  have seen the largest period effects. As a result of these changes, gender differences in location preferences have narrowed over time, and this is likely to have contributed to the recent closing of the gender gap in alcohol consumption and harm , 10. OneOur findings also suggest that the recent growth in the share of off‐trade drinking reflects a particular growth of drinking in non‐social settings. This is driven by older cohorts, while more recent cohorts appear much less likely to engage in non‐social drinking at home. This has implications for public health because, while drinking in a social setting is often linked to enhancing positive emotions, drinking in a non‐social setting (particularly solitary drinking) is associated with coping with negative emotions . MoreoveThe key strength of this analysis is that it is based on a very large sample, with drinking occasions data from over 300,000 individuals across 19 years. Importantly, the use of Alcovision data allows for aggregated trends to be disentangled into their component parts, which reveals nuances that would not otherwise be revealed in other data sources . However, there are some limitations. First, our data use quota sampling from an online panel, which can lead to biases , 40. SecWith regard to policy, policymakers may seize the opportunity of large‐scale and long‐term changes in the on‐trade sector to shape policy in ways that benefit public health. This may include a gradual reduction in overall alcohol availability but also targeted reductions in venues that promote heavier drinking and increases in venues that promote moderate consumption and minimise harm , 42. In Iain Hardie: Conceptualisation; formal analysis; methodology; writing ‐ original draft. Alessandro Sasso: Data curation; writing ‐ review and editing. Petra S. Meier: Conceptualisation; funding acquisition; project administration; writing ‐ review and editing. John Holmes: Conceptualisation; funding acquisition; project administration; writing ‐ review and editing.The authors declare no conflict of interest.As this was an analysis of secondary data no university ethical approval was required. Use of the data was allowed under the terms of the contract and non‐disclosure agreement between Kantar and the Universities of Sheffield and Glasgow.Appendix S1. Supporting Information.Click here for additional data file.


Mandrillus leucophaeus), a largely unstudied monkey species. We collected data from the birth to the death of the infant on maternal and alloparental care towards the newborn across three phases: pre-mortem, post-mortem, and post-mortem cannibalism. The mother maintained high levels of grooming after the infant’s death. Both the mother and other group members interacted with the dead baby by trying to engage its gaze. Two days after the death, the mother started to eat the corpse until it was almost completely consumed; there was no sharing with other group members. Although we cannot draw firm conclusions about potential benefits of the mother’s behavior, this observation on drills adds a piece to the puzzle of thanatological behaviors and cannibalism in primates.Comparative thanatology includes the scientific study of death in non-human animals, which involves emotional, social, and exploratory responses of individuals and groups towards corpses. Stillborn babies and dead infants often elicit maternal and alloparental care that can persist for days, weeks, or even months, especially in primates. After this period, cannibalistic acts can occur not only by groupmates but also by the mother. Such cannibalism has been reported both in captive and wild primate groups, suggesting that the phenomenon is evolutionary adaptive. Here, we report a case in drills (The online version contains supplementary material available at 10.1007/s10329-023-01075-8. Pan troglodytes, Anderson Loxodonta africana, Douglas-Hamilton et al. Delphinus capensis, Park et al. Macaca mulatta) was observed repeatedly performing such vigorous actions on an individual that had temporarily lost consciousness after being electrocuted on railway tracks  are semi-terrestrial, highly sexually dimorphic, forest-dwelling monkeys  was distributed around feeding time (08:00 h–12:00 h). Water was available ad libitum. All subjects . Video recordings were made with the aid of two video cameras , which allowed us to closely film the focal mother with her infant. As the frame covered about 4 m around the dyad, we also recorded behaviors that other group members directed towards the mother–infant pair, and used the videos to establish with precision when each drill might be able to interact with the dyad. A total of about 11 h of video was collected, coinciding with when the drills were visible to the observers. All behavioral patterns recorded are shown in Table S1.κ was never below 0.85; for specific behavioral categories analyzed, Cohen’s κ was: grooming/visual 88.4%, tactile 87.8%, olfactory inspecting 85.3%  and body contact/embracing 89.1%. To analyze time spent by grooming/inspecting and in body contact/embracing the newborn by the mother, we applied a Chi-square test. The exact Friedman test was employed to assess whether grooming/inspecting and body contact/embracing by the group members towards the mother–newborn dyad differed across the three observation phases ; in the case of a significant difference, we followed up with the Dunnett's multiple comparison test (post hoc test with Bonferroni correction). Statistical analyses were performed using SPSS 20.0.Two observers (authors APN and GC) independently analyzed 2 h of videos to assess inter-observer agreement . The newborn had appeared not to be in good health, as the mother had to actively hold him; he did not grasp her fur or reach the nipple. Although during the first 6 days no aggression towards the baby was observed, we cannot exclude that infanticide took place. The mother and other group members interacted with the corpse for 2 days (post-mortem phase) Table . On SeptSeptember 2nd—post-mortem phase (video 8:32–11:40)—At 8.42 we observed Kumasi holding and dragging the baby’s corpse while avoiding Chepo  (Video 1). She grooms it (Video 2) while shunning another adult female, Efuru, who is interested in it. At 9:30 two young adult males (Ndolo and Obudu) try to engage the dead baby’s gaze ; Chepo prevents Ndolo from approaching Kumasi and the dead infant (Video 4). At 9:57, Efuru grooms the dead infant (Video 5). At 11:26, Kumasi closely sniffs the corpse, while Ndolo approaches Kumasi, touches the baby, and makes nose-to-nose contact with the mother (Video 6). At 11:33, Obudu approaches Kumasi, makes nose-to-nose contact with her, and tries to engage the baby’s gaze. When Obudu touches the baby, the mother moves away, dragging it. Obudu aggressively pushes the mother twice, and Chepo approaches Kumasi and tries to engage the dead infant’s gaze. Some females try to make nose-to-nose contact with the mother while touching and inspecting the corpse. (video 17:06–17:20)—Kumasi holds and licks the baby (17:06–17:11). At 17.17, Atu  tries to steal it but Kumasi protects it; then she grooms and explores its head and limbs, until 17:20.September 3rd—post-mortem phase (video 10:20–12:03)—Kumasi holds the baby while feeding (10:20–10:53). At 11:00, Kumasi starts a reciprocal grooming session with Kwai , with Ndolo nearby, sniffing the baby. At 11:02, Kumasi starts grooming corpse. At 11:15, Atu and Ricardo, beside Kumasi, and look at and sniff the baby. At 11:23, Kumasi sniffs and grooms the corpse while protecting it from approaches of the males.(Video 17:03–17:54)—At 17:09, Kumasi attacks Atu twice, and after which Atu presents her rear to Kumasi. At 17:10, Kumasi starts grooming her baby. At 17:23, she jumps onto a branch and, for the first time, loses her grip on the corpse, which falls down to the ground (Video 7). At 17:24, Obudu throws the corpse away and drags it while spinning around (Video 8). Obudu and Kumasi alternate in dragging around and spinning the corpse. Post-mortem cannibalism phase—At 17:35, Kumasi starts eating the head of the baby; this lasts 1 min 30 s (Video 9). At 17:36, Obudu approaches the corpse and sniffs it; Kumasi avoids him. Obudu sits near Kumasi, while she continues feeding on the corpse (head and abdomen) for 5 min 45 s. At 17:39, Obudu tries to steal the corpse, but Kumasi fends him off. At 17:41, Kumasi continues feeding on the abdomen for 6 min 30 s. In the next 4 min, Obudu tries to sniff the corpse but Kumasi avoids him. At 17:46, Kumasi runs away from Kara  with the corpse. At 17:47, Kara sniffs the corpse for 2 min 16 s. Kumasi feeds on the corpse for 4 min and 30 s.September 4th day 3—Post-mortem cannibalism phase (video 10:03–11:16)—At 10:03, Kumasi feeds on the corpse for 17 min. (Video 17:00–17:30)—At 17:24, Kumasi feeds on the corpse for 4 min 25 s.χ2 = 1.32, df = 1, p = 0.251). During the death phase the mother showed more GR_IN than BC_EM ; conversely, during the post-mortem cannibalism phase the mother’s amount of time spent in BC_EM was significantly greater than GR_IN   and contact/embracing (BC_EM) by the mother towards the newborn. The time spent in GR_IN and BC_EM did not differ during pre-mortem phase . However, the frequency of GR_IN directed by other group members to the mother differed across the three phases . GR_IN was slightly though non-significantly more frequent during the pre-mortem compared to the post-mortem phase (Dunnett's test p = 0.057); no differences were found between the other conditions , with BC_EM significantly more frequent during the pre-mortem compared to the post-mortem cannibalism phase (Dunnett's test p = 0.003) being the only significant difference  of the corpse may indicate attempts to get a reaction from the baby. Interestingly, other group members also tried to engage the gaze of the dead infant. This observation recalls reports that both monkeys and apes often inspect the face and/or eyes of recently deceased individuals, possibly to detect the absence of eye movements . It is difficult to say if the discarding was intentional or not; however, until then the mother had never separated from the corpse, and immediately after discarding it both the mother and an adult male alternated in dragging it around. Regardless of its underlying motivation, this behavior appeared to signal a shift in the mother’s attitude towards her baby, including a significant reduction in grooming and inspection of the corpse Supplementary file2 (XLSX 10 KB)Supplementary file3 (MP4 8656 KB)Supplementary file4 (MP4 9288 KB)Supplementary file5 (MP4 12524 KB)Supplementary file6 (MP4 15420 KB)Supplementary file7 (MP4 25099 KB)Supplementary file8 (MP4 11062 KB)Supplementary file9 (MP4 12549 KB)Supplementary file10 (MP4 4508 KB)Supplementary file11 (MP4 8035 KB)Supplementary file12 (MP4 6268 KB)Below is the link to the electronic supplementary material.


Laparoscopic videos are increasingly being used for surgical artificial intelligence (AI) and big data analysis. The purpose of this study was to ensure data privacy in video recordings of laparoscopic surgery by censoring extraabdominal parts. An inside-outside-discrimination algorithm (IODA) was developed to ensure privacy protection while maximizing the remaining video data.IODAs neural network architecture was based on a pretrained AlexNet augmented with a long-short-term-memory. The data set for algorithm training and testing contained a total of 100 laparoscopic surgery videos of 23 different operations with a total video length of 207 h (124 min ± 100 min per video) resulting in 18,507,217 frames . Each video frame was tagged either as abdominal cavity, trocar, operation site, outside for cleaning, or translucent trocar. For algorithm testing, a stratified fivefold cross-validation was used.The distribution of annotated classes were abdominal cavity 81.39%, trocar 1.39%, outside operation site 16.07%, outside for cleaning 1.08%, and translucent trocar 0.07%. Algorithm training on binary or all five classes showed similar excellent results for classifying outside frames with a mean F1-score of 0.96 ± 0.01 and 0.97 ± 0.01, sensitivity of 0.97 ± 0.02 and 0.0.97 ± 0.01, and a false positive rate of 0.99 ± 0.01 and 0.99 ± 0.01, respectively.IODA is able to discriminate between inside and outside with a high certainty. In particular, only a few outside frames are misclassified as inside and therefore at risk for privacy breach. The anonymized videos can be used for multi-centric development of surgical AI, quality management or educational purposes. In contrast to expensive commercial solutions, IODA is made open source and can be improved by the scientific community. To achieve this objective, we used computer vision to develop and validate an algorithm that discriminates between inside and outside positioning of the laparoscopic camera.In the era of big data and the ever-increasing use of artificial intelligence (AI) in surgical procedures , patientTo overcome this video shortage, we have developed and validated an inside-outside-discrimination-algorithm (IODA) that discriminates the laparoscopic camera placement inside and outside of the abdomen. As a result, IODA helps to ensure data privacy in video recordings of laparoscopic surgery by censoring extraabdominal parts that may identify patients or personnel while also maximizing the remaining video data.There has been previous work to anonymize videos in the operating room in general. For example, Flouty et al. created a R-CNN network that detects faces in videos and consequently blurs them with a recall of up to 93.45% . DisadvaBy anonymizing laparoscopic videos based on inside and outside scenes, they can be safely used for big data analysis, such as surgical AI, quality management or educational purposes while immensely reducing the effort of data collection.Is it possible to reliably discriminate between inside and outside frames of laparoscopic videos using IODA based on deep neural networks?Does additional training information, such as classification of trocars, translucent trocars or outside for cleaning, improve algorithm performance?Where does the algorithm fail and does this result in privacy impairment?To realize this aim, the following research questions were investigated:IODA has been developed to discriminate between the camera view of the inside of the abdomen and the camera view of the outside parts. Two different computer vision algorithms were developed. They share the same architecture and only differ in the number of classes they can discriminate against. One algorithm discriminates between a binary outcome , and the other one considers five classes Fig. , two forThe neural network architecture is based on the work of Bodenstedt et al. . As a baFollowing the modified AlexNet is a stateless long-short-term-memory (LSTM). The aim of using an LSTM is that usually in a laparoscopic video each class  appears for an extended time and usually not as an isolated frame. Indeed, at a frame rate of 25 frames/s, an individual frame is 0.04 s long. Going from inside the abdominal cavity to outside and back in such a short time frame is very unlikely. A stateless LSTM was chosen because it analysis a single sequence of frames for correlations, but does not take into previously seen sequences. On the contrary, stateful LSTMs would memorize all sequences seen in training and are therefore more commonly used for phase recognition of laparoscopic videos, where this information is of importance . Lastly,Standard metrics that are commonly used work best on balanced class distributions. In the course of annotation, it became apparent that the two classes inside and outside are not balanced. Thus, the imbalanced class distribution made an introduction of a better fitting metric necessary. We opted for the Focal Loss, which adds a modulating term to the cross-entropy to focus learning on not only imbalanced classes but specifically hard to classify classes . In partThe data set contains a total of 100 laparoscopic surgery videos with 23 different operation types distributed over four categories: upper gastrointestinal, cholecystectomy, colorectal, and miscellaneous. In total, this amounts to 207 h of video . Consisting of 18.6 million frames, of which only 1 frame /second  was used to validate the algorithm in order to reduce computation time. The video files cover a range from short procedures, e.g., diagnostic laparoscopies, to extended procedures like laparoscopic-thoracoscopic esophagectomies performed at Heidelberg University Hospital. Table For the data annotation, the original procedure video was cut into ten minute sections and manually annotated by a medical expert using the annotation software Anvil . Two maiFor algorithm training, we used a five-fold stratified cross-validation. Five equally sized sets of 20 videos were formed and alternated to form the training and test sets. To ensure that these sets are as homogeneous in total video length and operation types as possible, the original data set was manually stratified into the five sets  with 2 AMD 7352 CPUs  and 6 NVIDIA A40 GPUs . The algorithm was written in python 3.9  using thStatistical analysis of the results is done via F1-score, sensitivity, and specificity of the outside class. The F1-score is chosen as it is the harmonic mean of precision and recall (sensitivity in the binary case) and hence a good overall metric for classification model performance. Sensitivity of the outside class indicates whether all outside frames are detected as outside, and is therefore important in terms of privacy protection. Any outside frame not detected may pose a privacy risk. Specificity of the outside class on the other hand shows how much of the inside frames are misclassified as outside. Specificity should be high to reduce the loss of valuable frames which are falsely censored.We manually annotated 15,392,966 frames as inside and 3,202,290 frames as outside. For our multiclass experiment these frames were divided into inside abdominal cavity  and trocar  as well as outside with outside no cleaning , outside for cleaning , and translucent trocar , as depicted by Fig. When trained for binary classification, IODA matched the annotation in 611,061 out of 616,113 (99.18%) inside frames and 123,757 out of 128,079 (96.63%) outside frames Fig. . Figure In the multiclass experiment, the predictions for “abdominal cavity” match the annotation in 601,161 out of 605,771 (99.24%) frames. For “trocar” 10,342 frames are annotated of which are almost in equal parts predicted as “trocar”  and “abdominal cavity” . For “Outside for cleaning” 8,061 frames are annotated of which 1,036 (12.85%) frames are predicted as “Outside for cleaning,” while 6,242 (77.43%) frames are predicted as “Outside.” For “Outside” 119,541 frames are annotated of which 114,887 (96.10%) frames are predicted as “Outside.”For “translucent trocar” 477 frames are annotated of which none are predicted as such, 206 (43.19%) frames are predicted as “trocar” and 196 (41.09%) frames as “abdominal cavity.”Out of all misclassified frames by our algorithm, there were three sequences (once 2 min and twice 15–20 s). Other than that, misclassification happened mostly in single or a series of few frames. Fig. In order to provide the algorithm with a sample of laparoscopic videos as representative as possible, 23 different surgery types and a total of 100 surgeries were selected. Since the majority of a laparoscopy is situated intraabdominally, there is an inevitable class imbalance between the inside and outside classes. Regarding the outside classes, there is also high imbalance toward the class “Outside no cleaning,” which is caused by quite long sequences before and after the actual laparoscopy, where video recording was already running or was still running.A striking feature of the analysis of discrepancies between manual annotation and algorithm is that the transition frames between inside and outside are especially critical and prone to errors. After analyzing the misclassified frames, especially in the multiclass experiment, it becomes apparent that the algorithm struggles with transitional areas between the camera view of the abdominal cavity and the trocar: 46.2% of frames predicted as “abdominal cavity,” 40% as “trocar.” Most probably it is caused due to our set annotation rules. The camera view of the circle and, depending on the angle, elliptical shaped trocar makes it difficult to precisely determine when it transcends 50% of the screen. Despite that all frames have been annotated to the best of the annotator's abilities, it can’t be guaranteed that the view of a category in all frames is approximated correctly. Another hurdle of the multiclass experiment is the unbalanced sampling; while frames of “abdominal cavity” make up the most part, there are only 477 used frames of a translucent trocar. The “Outside for cleaning”-category was initially intended to be used in future research projects to analyze the quantity of “Outside for cleaning”-phases and allow drawing conclusions about the complexity of the operation, the surgeon’s skill level and adapt the assisting systems. Due to the fact that this category is based on an intention, it creates a massive hurdle for our algorithm. The long-short-term memory sequences were chosen to be 32 frames, equaling 32 s of consecutive videos, which might not be long enough such that an outside sequence contains the cleaning specific activities. This is reflected in the results, where 77.4% of frames that are annotated as “Outside for cleaning” are predicted as “Outside no cleaning.”To ensure the goal of privacy protection, it is of most importance to correctly predict outside frames as “Outside,” which is reflected by a high specificity for “Outside.” To apply our results to a practical example in case of the binary experiment: for a specificity of 99.2%, in an 1-h laparoscopic video the time span of 21 s is at risk to be falsely predicted as “Inside” while the camera view shows an outside part, while also taking into account that the video consists of 17.2% outside frames. On the other hand, the sensitivity of 96,6% results in 25 s of video data of a 1-h laparoscopic video are at risk to be lost, because it is classified as “Outside” and therefore anonymized while the camera view correctly shows the inside of the abdominal cavity. The results of the multiclass experiment show similar values as 17 s are at risk to be falsely predicted as “Inside” and 25 s are at risk to be lost.While a human annotator can adapt to rare and special events, our algorithm had difficulties to classify these. Figure On the other hand, reviewing the misclassified frames showed the value and consistency of our algorithm. After checking discrepancies between IODA and the human annotator, we found obvious wrong human annotations: once because of an annotation software problem, where the annotation of a short phase had been deleted and twice because the annotator simply overlooked a short outside section. Thus, in expectation of an ever-growing database, IODA can already be expected to have an advantage and to be superior in consistency to a human annotator.Also, noteworthy is the time needed for annotating the video, when comparing the human annotator and the computer algorithm. Figure In the ever-increasing digitalization, it may be possible to utilize our developed algorithm to its full potential. Due to the massively increasing video data in the clinical workspace, we would be able to build a wide and diversified database, while ensuring patients privacy protection. These anonymized videos can then be used for surgical AI development, quality management, or for educational purposes, Fig. As of now, IODA runs with 45 frames per second on a hardware setup with a single NVIDIA A40 graphics card. Even if image loading and video transfer may add additional delay, the algorithm is thus suitable for “real-time” application within the operating room. This could be realized by using a medical pc with a video capture card that is connected to the video output of the laparoscope. However, the software that captures the video stream, hands it over to IODA, and displays the final video stream and potentially a graphical user interface would still need to be implemented for intraoperative real-time application.In future studies, the applicability of our algorithm on other operating centers with different color schemes of surgical drapes, skin and operating room surrounding, and more different operation types should be investigated. Larger data sets are essential to improve the performance of the algorithms, ideally with addition of medical device sensor data to complement manual reference annotations. Also, to speed up annotation processes, the development of time and cost-effective annotation tools should be realized. Another idea to explore that might improve the performance of IODA is a bidirectional training. Training IODA on forward and backward playing videos could increase the available data and the variability of trained scenes. Also, as explained in the methods section, the LSTM architecture of the network was chosen to take the temporal component into account, because usually each inside or outside scene is at least a couple of seconds long. In addition, a rule-based post-processing filter could be implemented that removes IODA outliers of a few frames by changing the class of very short sequences  to the surrounding class.Our Inside-Outside-Discrimination-Algorithm IODA allows for privacy protection when recording laparoscopic video data. Implementing this kind of deep learning into surgical video data sets holds the potential to immensely improve the quality and especially the quantity of available video data for secondary use.The next step will be a prospective evaluation within a real time setting in the operating room.