Despite their importance, accurate prediction of MSA andH2SO4 from DMS oxidation remains challenging.With comprehensive experiments carried out in the Cosmics LeavingOutdoor Droplets (CLOUD) chamber at CERN, we show that decreasingthe temperature from +25 to −10 °C enhances the gas-phaseMSA production by an order of magnitude from OH-initiated DMS oxidation,while H2SO4 production is modestly affected.This leads to a gas-phase H2SO4-to-MSA ratio(H2SO4/MSA) smaller than one at low temperatures,consistent with field observations in polar regions. With an updatedDMS oxidation mechanism, we find that methanesulfinic acid, CH3S(O)OH, MSIA, forms large amounts of MSA. Overall, our resultsreveal that MSA yields are a factor of 2–10 higher than thosepredicted by the widely used Master Chemical Mechanism (MCMv3.3.1),and the NOx effect is less significantthan that of temperature. Our updated mechanism explains the highMSA production rates observed in field observations, especially atlow temperatures, thus, substantiating the greater importance of MSAin the natural sulfur cycle and natural CCN formation. Our mechanismwill improve the interpretation of present-day and historical gas-phaseH2SO4/MSA measurements.Dimethyl sulfide (DMS) influences climate via cloud condensationnuclei (CCN) formation resulting from its oxidation products (mainlymethanesulfonic acid, MSA, and sulfuric acid, H Understanding the OH-initiated DMS oxidationprocess inthe atmosphere is essential to properly describe the process chainfrom phytoplankton DMS emissions to climate effects. Theythus affect the formation, optical properties, and lifetime of marineclouds,8 influencing cloud radiative propertiesand therefore climate.16Dimethyl sulfide (DMS) is emitted intothe atmosphere by marinebacteria and as a result of the degradation of dimethylsulfoniopropionate(DMSP) produced from phytoplankton.18 Understanding how gaseousMSA contributes to this ratio is important in understanding the impactof DMS oceanic emissions leading to the formation of low-volatilityspecies via oxidation. The multiphase chemical mechanism is complex,and the yields of H2SO4 and MSA depend on temperature19 as well as atmospheric composition. Moreover,field measurements of gas-phase MSA and H2SO4 show a wide range of concentrations.23The ratioof particulate MSA to non-sea-salt sulfate varies between0.05 and 0.75 and is usually below 0.5.12 Atmospheric H2SO4 is formed from sulfur dioxide(SO2) oxidation, which comes from anthropogenic and volcanicemissions as well as DMS oxidation. It follows that the ratio of H2SO4 to MSA (H2SO4/MSA) isan important indicator of both regional variations and anthropogenicperturbation in both current and historical samples. Furthermore,both species may participate in new particle formation13 and CCN formation processes together with iodine oxoacids and ammoniain polar regions.25 Consequently, a quantitative,mechanistic understanding of the DMS oxidation mechanism(s), especiallythe resulting H2SO4/MSA, is essential to furtherour understanding of their roles in climate change.Atmospheric MSA is formed primarily from DMS oxidation, withhighconcentrations observed in polar regions.28 Recent experimental work and in situ field observations have shownthat autoxidation plays an important role in the oxidation of DMSat higher temperatures (>0 °C), proceeding through the formationof hydroperoxymethyl thioformate  viaisomerization of the methylthiomethylperoxy radical , which is the primary product of DMS hydrogenabstraction.32 However, subzero conditions (<0 °C) are challenging to investigateexperimentally and so have received less attention. Hydrogen abstraction,both by OH and via isomerization (autoxidation), is suppressed ata lower temperature, and the OH addition pathway is known to dominate,as shown in previous studies.35 Finally, wall reactions can beproblematic in the laboratory, and their effects on the DMS oxidationexperiments have been unclear so far.27DMS oxidationhas been studied extensively with a wide array ofinstrumentation. However, chamber and flow-tube experiments have haddifficulties reproducing DMS oxidation under atmospherically representativeconditions, leaving us with significant gaps in our chemical understanding.39 and aqueous-phase processes40 to close the gaps between themodeled and measured oxidation products, suggesting reduced importancefor OH-initiated DMS oxidation. However, even with recent revisionsbased on experimental findings, models with current state-of-the-artgas-phase mechanisms underestimate ambient MSA.40 Here, we show that those mechanisms overestimate H2SO4/MSA by a factor of 2–10 throughout the ambient temperaturerange. The mechanism adopted in this study is similar to the gas-phasemechanism in the study of Wollesen de Jonge et al.,41 which revised the gas-phase chemistry (MCM) to explaintheir high particulate MSA.Model studies have addressed the importance of halogen chemistry13 under conditionsthat closely match the marineboundary layer (MBL) with an extensive suite of instruments. We investigatedthe gas-phase OH-initiated DMS oxidation over a wide temperature range(−10 to +25 °C) and present a revised mechanism describinggas-phase DMS oxidation. In addition to H2SO4 and MSA, we quantified numerous intermediate products, includingthe key intermediate methanesulfinic acid (CH3S(O)OH, MSIA),and used them to evaluate and constrain the mechanism. In additionto the gas-phase chemistry, we quantified semiempirical rate coefficientsfor the heterogeneous formation of the important products dimethylsulfoxide (CH3S(O)CH3, DMSO) and dimethyl sulfone(CH3S(O)2CH3, DMSO2).We designed our experiments such that the particle condensation sink(CS) is negligible. In CLOUD and most experiments, these multiphaseprocesses occur on the chamber walls,41 but they canalso occur on or within aerosols and cloud droplets in the atmosphere.We investigated the effects of temperature and NOx on gas-phase OH-initiated DMS oxidation. Both our experimentsand our revised oxidation mechanism closely match ambient gas-phaseH2SO4/MSA, and together they provide a quantitativeunderstanding of this critical natural biogeochemical process.We performed experiments in theCLOUD chamber at CERN3. The chamber is surrounded by an insulated thermal housing,which maintains high-temperature uniformity and stability, and itcan be operated over a wide range of temperatures (from −70to +100 °C) and relative humidity (from below 1% to above 90%).Ultrapure synthetic, humidified air (cryogenic 79% N2 and21% O2) and a slight overpressure minimize contaminantsin the chamber. All trace gases  haveindependent gas lines connected to the chamber to avoid reactionscaused by mixing in the gas lines before injecting into the chamber.Dry nitrogen was used to dilute DMS, NO2, and O3 from standard high-concentration gas bottles before reaching thechamber to obtain close to atmospheric concentrations.The CLOUD chamber isan electropolished stainless steel cylinder with a volume of 26.1m3). The distributionof UV lamps and laser in the chamber make the gas-phase oxidationproducts  form uniformly in a few minutes. An LED sabre(LS3) at 385 nm was used to photolyze NO2 producing NO.Sulfur dioxide (SO2) was measured with a high-sensitivitypulse fluorescence analyser ,ozone with a UV photometric ozone analyser , carbon monoxide using a nondispersion cross-modulationinfrared analysis method , and nitrogen oxidesNO with an ECO Physics CLD 780TR and NO2 with a CavityEnhanced Differential Optical Absorption Spectroscopy (CE-DOAS). TheSO2 monitor employed at CLOUD was unfortunately not ableto measure the formed SO2 from DMS oxidation because ofits high detection limit (0.5 ppb). A chilled dew-point mirror (EdgeTechInstruments) and a direct tunable diode laser absorption spectrometer were usedto continuously monitor the water vapor concentration.Four200 W Hg–Xe UV lamps at wavelengths between 250 and 450 nm with adjustable power and axenon fluoride excimer laser (UVX) at 248 nm were used to generateOH radicals via photolysis of ozone  and to reduce wall loss ratesof DMS oxidation products to establish a new steady-state condition.Temperature-ramping experiments were conducted at two temperatureranges (+25 to +10 and +10 to −10 °C) with different initialconcentrations of DMS, OH, and CO. The temperature ramps took a fewhours each, which is only slightly longer than the residence timein the chamber. Therefore, unlike in a typical oxidation experiment,steady states were not reached for each temperature in the temperature-rampingexperiments. As such, H2SO4-to-MSA ratios inthese experiments should not be used directly in other contexts becausethey are not measured in steady state. They can, however, be usedfor investigating the temperature dependence by simulating the fullconcentration profile at each point in time and then comparing themodel results with the experimental results.The OH-initiatedDMS oxidation experiment was conducted as follows:Before the oxidation experiments, the mixing fan speed was set to100% to enhance turbulent mixing in the chamber, thus reducing theconcentrations of oxidation products due to faster wall loss. Theinjection rates of ozone, DMS, and NO3–-CIMS), a bromide chemical ionization mass spectrometer coupled witha multischeme chemical ionization inlet (Br–-MION-CIMS),the gas-phase channel of a bromide chemical ionization mass spectrometerequipped with a Filter Inlet for Gases and AEROsols inlet (Br–-FIGAERO-CIMS), selective reagent ionization mass spectrometers(SRI-TOF-MS), and proton-transfer reaction time-of-flight mass spectrometer.The experiments were grouped into three sets depending on the availabilityof instruments and temperature. We conducted experiment set 1 at −10°C, experiment set 2 at +10 and −10 °C, and experimentset 3 at +25 and +10 °C, with relative humidity ranging from20 to 70%. NO3–-CIMS and PTR3 workedduring all of the experiments. However, the mode of PTR3 was changedfrom a regular H3O+ mode to NH4+ mode in experiment set 3. Br–-MION-CIMSmeasurements were only available in experiment set 1 and Br–-FIGAERO-CIMS measurements were only in experiment set 2. The conditionsof the experiments and relevant instruments are listed in Table S1.State-of-the-artinstruments were operated simultaneously to measure the gas-phaseconcentrations of DMS and its oxidation products. They were measuredby a suite of advanced mass spectrometers including a nitrate-ion-basedchemical ionization mass spectrometer (NO3O+-CIMS) provided the DMS concentration.The instrument is based on the design of the proton-transfer reactiontime-of-flight mass spectrometer (PTR3) described in Breitenlechneret al.43 DMS concentrations were calibratedwith a gas standard at specific conditions between experiments. Theconcentrations of DMS for the second experiment set were providedby the selective reagent ionization mass spectrometer (SRI-TOF-MS)described in detail by Canaval et al.44 We calibrated both instruments regularly between experiments witha standard gas mixture containing multiple volatile organic compoundsto account for any possible drifts in transmission efficiency or absolutehumidity dependency.A proton-transfer reaction time-of-flight massspectrometer 2OOH were measured with anitrate-ion-based chemical ionization mass spectrometer . The specially designed inletfor chemical ionization at the ambient pressure system and its calibrationand quantification procedures are well described by previous studies.47 We applied the same calibration coefficient C2SO4H = 4.13 × 1010 cm–3 per normalized signal  for the experiments carried outat +10 and −10 °C since charging efficiency does not varysignificantly in this temperature range. The uncertainty for NO3–-CIMS is mainly caused by H2SO4 calibration, below ∼50%; this uncertainty includesthe systematic error from calibration setup and statistic error. Alluncertainties for each species from the different instruments arelisted in Table S2. We estimate that MSAhas a collision-limited charging efficiency and strong binding energywith less fragmentation than H2SO4 based onthe cluster binding enthalpy calculated by quantum chemical methods(see Text S1.3 and Tables S3 and S4 fordetails). The measurement sensitivity of methanesulfonic peroxide(CH3S(O)2OOH) is lower than the maximum sensitivity,and the given concentrations represent its lower limits. The detailedestimation for MSA and CH3S(O)2OOH can be foundin Text S1.3.The concentrations of H2, methylthioformate (CH3SCHO), and methanesulfenic acid (CH3SOH) were measured either by an H3O+- or NH4+-CIMS.48 Different ionization schemes  were used in different experimentsas shown in Table S1. We determined theinstrument’s collision limit calibration factor by ionizing1 ppbv of hexanone from a gas standard diluted in air. Applying thecollision limit calibration factor to all compounds ensures lower-limitestimates for their concentrations. As shown in Figure S2, the independence of the concentration ratios determinedby both ionization methods  with the collision limitcalibration factor on sample gas humidity and temperature suggeststhat both DMSO and DMSO2 are very likely ionized at thecollision limit in both ionization modes. The lower-limit estimatesare therefore most likely their true concentrations. The comparisonbetween the two ionization methods at the same time can be realizedwith additional experiments performed with high ammonia concentrationin the chamber. These additional experiments have much higher DMS,O3, and NH3 concentrations than the OH-initiatedDMS oxidation experiments to investigate the formed particles at largersizes of around 100 nm. In contrast to the OH oxidation experimentswhose goal is to investigate the chemical mechanism, the goal of theadditional experiments with high NH3 is to investigatethe CCN potential of the formed particles. That is, the much higherconcentrations of DMS, O3, and NH3 facilitatesustained condensation that leads to larger particles. Additionally,the conducted voltage scan experiment in Figure S3 shows that the DMSO and DMSO2 hydronium-waterand ammonium clusters are stable against fragmentation at the chosensettings and that their proton affinity is high enough to even keepthe charge upon collision-induced fragmentation at higher voltages.Their uncertainties are estimated at around 20% in H3O+-CIMS and 50–80% in NH4+-CIMSwith the larger uncertainty of the collision limit sensitivity inthe latter. The reported concentrations of CH3SCHO andCH3SOH are lower-limit estimates also based on the resultsof the voltage scans. See Text S1.4 forthe detailed description.The concentrations of DMSO, DMSO–-MION-CIMS) and the gas-phase measurement of bromide chemical ionizationmass spectrometer equipped with a Filter Inlet for Gases and AEROsols(Br–-FIGAERO-CIMS)49 werethe primary instruments to detect MSIA and HPMTF. The peaks of MSIAand HPMTF measured by Br–-MION-CIMS can be foundin Figure S4. If neither instrument wasavailable due to instrument malfunction or absence in some experiments,NO3–-CIMS was used to measure MSIA andHPMTF. The instrument setup and operation of Br–-MION-CIMS and FIGAERO are described in Rissanen et al.50 and Lopez-Hilfiker et al.,49 respectively. In addition to ionization with Br–, we also detected both MSIA and HPMTF with NH4+ and H3O+-CIMS. While direct calibrations ofMSIA and HPMTF were not available, the intercomparison between thethree ionization modes and the use of quantum chemical calculationsprovide reasonable constraints on the ionization efficiency of thetwo species and hence their concentrations.A bromide chemical ionization mass spectrometercoupled with a multischeme chemical ionization inlet (Br–-MION-CIMS andBr–-FIGAERO(g)-CIMS using the MSA concentrationmeasured by NO3–-CIMS. Afterward, MSAcalibration factors in both instruments are used to estimate the lowerlimits of HPMTF and MSIA concentrations with high uncertainty. Thetraces shown in Figure S7 for MSIA fromNH4+- and H3O+-CIMS arecalibrated using the collision limit assumption. It is very likelythat if ionization does not occur at the collision limit with allprimary ion clusters with water, a strong water dependence would beobserved between the different modes. The apparent humidity independenceof the ratio of the MSIA concentration derived from the three differentionization schemes  suggests that the compound isdetected at the collision limit in these ionization schemes. However,the fragmentation caused by the electric field in the vacuum chamberalso affects the detection efficiency. The signals of MSIA and HPMTFin Br–-MION-CIMS might underly some fragmentationor other unaccounted losses in the instrument or inlet. Yet, the voltagescan results in Figure S8 show that MSIAis detected at maximum sensitivity in both H3O+ and NH4+-CIMS. Therefore, we use the MSIAconcentration from H3O+-CIMS with around 28%uncertainty due to the calibration and inlet and instrumental losscorrection. The signal of HPMTF is influenced by neighboring peaksand is divided into many water clusters in H3O+-CIMS, while this is not the case in NH4+-CIMS.Unfortunately, NH4+-CIMS was not available formany of the experiments, and the limit of detection in H3O+-CIMS was too high to use the data during the hereinanalyzed experiments with low concentrations. As such, we use thelower-limit estimation for HPMTF concentrations from Br–-FIGAERO(g)-CIMS. See Section S1.5 for the detailed description and estimations.We first derivedMSA calibration coefficients for BrThe average residence time in the CLOUD chamber was ∼1.3 hfor experiment sets 1 and 2. The reaction rates of oxidation productswere derived from steady-state measurements, which means that theinflow of all gases, the concentration of oxidants, and oxidationproducts were kept constant. Under steady-state conditions, the rateof change of oxidation products equals zero, and we can writepX is the oxidationproduct, Y typically is OH or O3, kYi are the reactionrate coefficients for the reaction of X and Y, and kloss is either the ventilationloss (2.1 × 10–4 s–1 in experimentsets 1 and 2) or wall loss that is listed in Table S2. All of the oxidation product concentrations were measuredat the steady-state condition. The OH concentration used in this studyis estimated from our box model, and its reactions involved in formingOH radicals are listed in Table S7.Therefore, we can get the productionrate Table S1). We combine the simulation and experimental results to evaluateand constrain the role of different DMS gas-phase oxidation pathwaysin MSA and H2SO4 formation. The chemistry mechanismwas generated with the Kinetic PreProcessor (KPP)51 and solved with the ordinary differential equation solverRODAS3 (Rosenbrock method of order 3).52 The concentrations of oxidation products are determined by the chemicalproduction and loss from gaseous chemistry, wall reactions, ventilationloss, wall loss, and the condensation sink (CS) to generate particlesin the CLOUD chamber. The measured temperature, relative humidity,DMS, O3, CO, NOx concentrations(Table S1), and O3 photolysisrate with high time resolution were used as input to the model. Thephotolysis rate of O3 for UVH at full intensity or 5 Wof UVX is around 6 × 10–5 s–1. The OH concentrations are adjusted by changing the UV light intensity,O3, and H2O concentrations. The CLOUD chamberventilation loss is mainly determined by the flush-out flow . Specieslike H2SO4, MSA, and hydrogen oxide radicalsare readily lost to the wall surface. We measured the lifetime ofall species (Table S2) in the dark decay and cleaning stage  toestimate the losses and applied them to our box model. With the increaseof fan speed from 12 to 100%, the wall losses increased by a factorof 1.5–4.6 for different species. The measured loss of specieslike methyl thioformate (CH3SCHO) in the cleaning stageis slightly larger than the ventilation loss caused by the flush-outflow. It suggests that the loss of CH3SCHO is dominatedby ventilation whose loss increases mildly with the increased fanspeed. Therefore, we added extra loss terms for dimethyl sulfoxide(CH3S(O)CH3, DMSO), dimethyl sulfone (CH3S(O)2CH3, DMSO2), and CH3SCHO to fit their time evolutions in the cleaning stage. Theparticle condensation sink measured in this study is smaller than1 × 10–5 s–1, which is negligiblecompared to other loss processes. The detailed description of chemistrymechanisms used in the box model can be found in Text S2.In this study, a numerical model with zerodimension was set up and used to simulate DMS oxidation processesat different initial conditions 2OOH, CH3SCHO, and CH3SOH, as shown in the figures. Some speciesare quantified with proper calibration factors, while species likeCH3S(O)2OOH, HPMTF, CH3SOH, and CH3SCHO (by NH4+-CIMS) are lower-limitestimates due to the lack of authentic standards or generation methods.A more detailed description is given in the Text S1.3) concentrationsstabilized. The time sequences of different DMS oxidation productsshow different behaviors. The evolution of H2SO4, MSA, MSIA, HPMTF, CH3S(O)2OOH, and CH3SOH is consistent with the expected time response of gas-phaseproduction through OH oxidation (with lights on) and wall loss. Themeasured concentration reaches their maxima in the order of a fewminutes rather than a few hours like aqueous-phase reactions. TheCH3SCHO evolution is consistent with gas-phase productionand loss to ventilation rather than the walls, which has a timescaleof ∼1.3 h (26.1 m3/330 lpm). DMSO shows a smallfractional, but large absolute, increase with photochemistry, yetonly a modest fractional wall loss. DMSO rapidly reaches a steadystate, while DMSO2 decreases slowly and continuously fromthe onset of the run, associated with the slowly decreasing productof the DMS and O3 concentrations.The time traces in Figure S11 reveals that DMSO and DMSO2 have a sourcefrom the wall, which has also been shown in a previous study.27 As described in the 2 when the UV lights are on. Inturn, DMSO2 is long-lived in the gas phase and so has minimalinfluence on the chemistry. DMSO is also produced on the walls, butonce OH is present, both gas-phase production and loss of DMSO viaOH far exceed the wall production rate .2SO4 are far less abundantthan the first-generation oxidation product CH3SCHO, butMSA and H2SO4 have rapid wall loss, as do theirprecursors, such as MSIA, CH3SOH, and HPMTF. Consideringthe wall loss rate, we find that the production rates for MSA (3.2× 104 s–1) and CH3SCHO(4.5 × 104 s–1) are similar, withuncertainties at around 50 and 20%, mainly caused by their measuredconcentrations. We seek these production rates along with molar yieldsand branching ratios. To constrain the production rates, we need aphotochemical model of the chamber and the DMS oxidation sequence,including the walls.As shownin Table S2 show that MSA and H2SO4 have the same values,allowing a direct comparison of the two species’ concentrations.As shown in 2SO4, which cannot be explained when assuming that MSAis exclusively formed from the hydrogen abstraction channel  and CH3,55 but mayalso react with O2 to produce MSA. This pathway and itsreaction rate coefficients are not yet well understood. Therefore,in the box model, we add the pathway proposed by Yin et al.,57 Lucas et al.,58 andHoffmann et al.40 that MSIA reacts withOH or NO3 radicals forming methyl sulfonyl radicals (CH3S(O)2) as an intermediate, which then either decomposesto SO2 or reacts with O3 to form MSA (via CH3SO3 reaction with HO2) and SO3, instead of producing SO2 only. A recent study also appliedthis pathway to a multiphase model41 toexplain the observed high particulate MSA/sulfate at 0 and 20 °C.The measured wall losses in 55 suggested that the reactionof MSIA and O3 is unlikely to be competitive with MSIAand OH because of the large discrepancy between these two reactionrate coefficients. Even at high O3 concentrations (ca.100 ppbv), the first-order reaction rate coefficient of MSIA by O3 is 4.4 × 10–10 s–1, which is much smaller than the first-order reaction rate coefficientof MSIA by OH at 2.8 × 10–4 s–1 . Therefore, the critical conclusion is that we wouldsuggest that MSIA reacts with OH, producing both MSA and H2SO4. Thus, both the addition and abstraction pathwaysof DMS oxidation form MSA in the gas phase, explaining the higherMSA concentrations observed in field observations and CLOUD experiments.Lv et al.k3wallDMS + O and k3wallDMSO + O. Using anumerical model  toour DMS oxidation mechanism 1 by dire2SO4, CH3S(O)2OOH, and DMSO concentrations in –-FIGAERO-CIMS to HPMTF due to a stronger declusteringprocess compared to the maximum sensitivity compounds (see Text S1.5 for details). The discrepancy betweenthe modeled and measured HPMTF can be varied from 6 to 14 by applyingdifferent reaction rate coefficients of the isomerization of MSP.As shown in The modeled MSA, H2 concentrationsand their qualitative behaviors 2OOH are high, their influences on our mainconclusion—that MSA likely forms substantially via gas-phaseoxidation of MSIA by OH—are negligible since they are not thedetermining species in this argument.When we exclude the wall reaction from themodel, the resultingvast difference between the modeled and measured DMSOehaviors 3 indicat2, MSIA, MSA, and H2SO4), we conclude that the mechanism presented here can representDMS oxidation by OH radicals in the marine atmosphere.Overall, the underestimatedcalibration factor can explain thediscrepancy between the modeled and simulated HPMTF. Based on theclose agreement between the model and measurements for major oxidationproducts , degradation of MSIA (which is not fullyunderstood), and (4) peroxy radical isomerization of MSP in abstractionpathway 1b. All of these, especially the thermal decomposition, influenceH2SO4/MSA. We plot H2SO4/MSA versus temperature in x, respectively. Thepurple symbols are ambient data, and the black lines are box-modelsimulations with various mechanisms. The CLOUD data come from twoseparate temperature-ramping experiments, one cooling from +25 to+10 °C and the other from +10 to −10 °C, both withoutNOx. In 2SO4/MSA rangesfrom 0.3 to 1.3 (−10 to +10 °C) and 1.4 to ∼11(+10 to +25 °C), decreasing exponentially with decreasing temperature.Ambient observations of gas-phase H2SO4/MSAvary from 1 to 17 at Mace Head, Ireland (during Summer)21 and from 0.3 to 3 in polar regions (from Februaryto August).12 These observations can bereproduced by the inferred experimental temperature dependence. Theambient concentrations of DMS, O3, OH, and NOx during the measurements of H2SO4/MSA from Beck et al., presented in 2SO4 concentrationsreported in Beck et al.’s observation and our experiments.However, we find that the ratio of H2SO4/MSAis mainly determined by temperature  the branching ratio of addition/abstractionat the first step of DMS oxidation by OH radicals, (2) thermal decompositionof CHperature 4 instead2SO4/MSA with the OH-initiated DMS oxidation mechanismdeveloped here(solid line) and compare it to the gas-phase mechanism from MCMv3.3.159 (dashed line) and Hoffmann et al.40 (dotted line) in 3S(O)2 and CH3SO3 in abstraction pathway 1a, whichcontains an exponential temperature dependence that largely determinesH2SO4/MSA. However, our mechanism shows muchbetter agreement with the observed H2SO4/MSAcompared to the other two mechanisms. This is because the reactionof MSIA with OH radicals contributes more to MSA production and consequentlyreduces H2SO4/MSA rather than only contributingto SO2 formation, as e.g., in MCMv3.3.1. Overall, the observedtemperature effect suggests a potentially greater role for MSA incolder regions in important processes such as new particle formationand growth, as our mechanism and observations show that the H2SO4/MSA ratio is smaller than 0.5 when the temperatureis below roughly +2 °C.We modeled the temperature dependence of Hx  influences OH-initiated DMSoxidation, for example, through bimolecular reactions between peroxyradicals (RO2) and NO. As shown in 2SO4/MSA from twoexperiments with NOx (red circles) agreeswith the temperature-ramping experimental results (green circles),indicating that NOx has a negligible effectcompared to the temperature sensitivity over this same range. TheNOx-ramping experiments in Figure S15 confirm that NO2 and NOonly slightly enhance H2SO4/MSA in contrastto the strong effect from temperature change. The measured H2SO4/MSA at +10 °C  and −10 °C increase by 54 and 100% as NO2 increases from 0 to 400pptv. The effect of NOx on HPMTF formationis not clear . We observe aslight drop of HPMTF (17%) and almost constant DMS in Figure S15A. However, Figure S15B shows a 100% increase in HPMTF and a 20% drop in DMS becauseDMS reacts with NO3 radicals. We cannot quantify the effectof NOx on HPMTF formation because of theinterference from N2O5 formed from the reactionof O3 and NO2, which has a close molecular weightto HPMTF.In addition to temperature, NO2SO4/MSA  is very sensitive toNO2 concentration varies dramatically as NO2 increases from 0 to 160 pptv. However, the modeled H2SO4/MSA from the other two mechanisms 2, because it excludesthe isomerization reaction of CH3SO2 producingCH3S(O)2 . The isomerization reaction is estimated with a constantvalue of ∼1 s–1 in previous studies,61 which is higher than the bimolecular reaction rate of CH3SO with NO2 (∼1.2 × 10–1 s–1 with a maximum 400 pptv NO2), althoughit lacks the temperature dependence.In MCMv3.3.1, the modeled H2SO4/MSA S16 is vex on product distribution is greatly diminished comparedto the MCMv3.3.1. Second, the key ratio H2SO4/MSA is substantially reduced (MSA is increased), with the absoluteratio and temperature dependence in the mechanism agreeing with boththe experimental data and ambient observations.Overall, the suite of simultaneouslymeasured key intermediateshelped us to adjust the previous DMS oxidation schemes. Our mechanismhas two major improvements. First, the influence of NOx, the distribution of oxidants including OH,NO3, halogen compounds,62 and available water for multiphase oxidation in aerosolsand droplets.63 In this study, we followed thekinetics of a suite of gas-phase reaction intermediates and finalproducts in DMS oxidation experiments by OH to investigate the effectsof temperature and NOx. Our results showa strong temperature dependence for DMS oxidation, especially theyields of oxidation products such as MSA.DMS oxidationin the atmosphere is affected by temperature, NO2SO4/MSA from OH-initiated DMS oxidation, especiallyat low temperatures (<0 °C). From the box-model results, itis clear that the inclusion of the gas-phase MSA formation mechanismvia oxidation of MSIA by OH improves the agreement between modeledand experimental results at low temperatures. When MSIA reacts withOH, it may produce CH3S(O)2 or another adductintermediate; regardless, both CH3S(O)2 andthe adduct intermediate decompose to SO2 or SO3 to form H2SO4 or react with O3 orO2 to form MSA. For both pathways, we can expect a similartemperature dependence.Our experimental resultsshow high MSA concentrations and reducedH29 leads to the HPMTF formation, which increasesH2SO4 production substantially through oxidationof HPMTF.30At low temperatures, the oxidation ofDMS with OH proceeds morevia the OH addition channel, forming abundant DMSO and MSIA, and consequently,a large amount of MSA. At high temperatures, the reaction rate ofthe OH addition channel decreases, which lowers MSIA and MSA formation,while the hydrogen abstraction channel becomes more important. Also,the predominance of MSP isomerization 41 and field observations17 since both MSA andH2SO4 participate in particle growth. Interestingly,NOx is far less influential than previouslythought. At −10 °C, H2SO4/MSA increasesby 100% after ramping up NO2 (from 0 to 400 pptv) and NO(from 0 to 8 pptv). But the observed change (red circles) is small(less than 50%) compared to the effect of changing temperature (aboutan order of magnitude when the temperature decreases from +10 to −10°C).Therefore, we propose that MSIA isimportant in MSA formation atlow temperatures, which can also be connected to the observed highparticulate MSA/sulfate in laboratoryTable S5, ourexperimentalMSA (0.2 to 1.5 × 107 cm–3) andH2SO4 (0.3 to 3 × 106 cm–3) concentrations formed from OH-initiated DMS oxidationexperiments conducted at −10 °C are in the range of fieldmeasurements. For example, the concentrations of MSA and H2SO4 measured in Ny-Ålesund station  range from 0.1 to 4 × 107 cm–3 and 0.2 to 7 × 106 cm–3, respectively.Aerosol concentrations also affect gas-phase MSA and H2SO4 concentrations because of their different aerosolpartitioning. However, the particle condensation sink in this studyis smaller than 1 × 10–5 s–1, which is only slightly larger than the values at Ny-Ålesund(∼4 × 10–4 s–1) andVillum (∼3 × 10–4 s–1).As shown in 2 and DMSO are important sulfur reservoirsin ourstudy. They can also be formed from wall reactions without OH radicals.Our simulations show that wall reactions are the major source of DMSO2 but have a limited role for other oxidation products comparedto the gas-phase reactions (even DMSO). In the atmosphere, analogousto the wall of the chamber, cloud droplets and aerosol water couldplay a similar role. Therefore, the observed high concentrations ofDMSO2 (40–120 pptv) and DMSO (3–18 pptv)at night over the Arabian Sea64 and PacificOcean65 may be associated with multiphaseDMS oxidation.DMSOFigure S18, terminal products MSA andH2SO4 accumulate in parallel over time, ultimatelyconstituting the dominant reaction products. DMSO, MSIA, CH3SCHO, and CH3SOH are the precursors for MSA and H2SO4, reaching a steady state during the first dayof simulation. HPMTF is a precursor for SO2, and after1 week, both reach high concentrations and slowly approach steadystate. Field measurements indicate high concentrations of HPMTF (upto 50 pptv in the marine atmosphere32)and its possible participation in particle formation. Accounting HPMTFchemistry in a global chemistry transport model66 results in a significant decrease in boundary layer levelsof SO2 and H2SO4. Novak et al.67 demonstrate that the rapid loss of HPMTF toclouds terminates DMS oxidation to SO2. This is importantat high temperatures. On the other hand, at low temperatures, HPMTFproduction is strongly reduced, and the main product becomes MSA viaMSIA, so the fraction of oxidized DMS leading to SO2 issignificantly lowered. The concentration of DMSO2, a terminalproduct of OH-initiated oxidation of DMS, remains low in the absenceof heterogeneous reactions. These simulations suggest that MSA maybe the dominant oxidation product of DMS oxidation for conditionsfound in the high-latitude marine atmosphere with low temperatures.The DMS oxidation lasts only a few hours in theCLOUD chamber,while it can be for a few days in the atmosphere depending on theconditions. To gauge possible atmospheric evolution (a few days),we simulated OH-initiated DMS oxidation over a long timescale (∼1week) at −10 °C, excluding walls and ventilation. As shownin 2SO4 in the remote atmosphere. Our observationof many intermediate products closes gaps between the measured andmodeled MSA. Specifically, MSIA and HPMTF are useful intermediatesthat serve as markers for OH addition and hydrogen abstraction channels,respectively. Therefore, measurement and proper calibration of thesetwo species become important in future laboratory experiments andfield observations for studying DMS. These findings improve our understandingof the atmospheric DMS oxidation process and its contribution to thenatural sulfur cycle and potentially the formation of biogenic aerosoland thus CCN.The agreement between the present chamber study, our model, andambient observations over a wide temperature range is consistent withOH-initiated DMS oxidation governing the formation of gas-phase MSAand H


Marine mammals are facing many threats that impact their ability to obtain energy to survive and reproduce. Much remains unknown about marine mammal bioenergetics, which hinders real-world applications to conservation and management. We surveyed the bioenergetic community to identify ‘key’ unanswered questions to help guide future marine mammal research efforts. Bioenergetic approaches are increasingly used to understand how marine mammal populations could be affected by a changing and disturbed aquatic environment. There remain considerable gaps in our knowledge of marine mammal bioenergetics, which hinder the application of bioenergetic studies to inform policy decisions. We conducted a priority-setting exercise to identify high-priority unanswered questions in marine mammal bioenergetics, with an emphasis on questions relevant to conservation and management. Electronic communication and a virtual workshop were used to solicit and collate potential research questions from the marine mammal bioenergetic community. From a final list of 39 questions, 11 were identified as ‘key’ questions because they received votes from at least 50% of survey participants. Key questions included those related to energy intake  and expenditure , energy allocation priorities, metrics of body condition and relationships with survival and reproductive success and extrapolation of data from one species to another. Existing tools to address key questions include labelled water, animal-borne sensors, mark-resight data from long-term research programs, environmental DNA and unmanned vehicles. Further validation of existing approaches and development of new methodologies are needed to comprehensively address some key questions, particularly for cetaceans. The identification of these key questions can provide a guiding framework to set research priorities, which ultimately may yield more accurate information to inform policies and better conserve marine mammal populations. Published by Oxford University Press and the Society for Experimental Biology.

Received April 12, 2022; Revised June 28, 2022; Accepted July 15, 2022
 Bioenergetics is the study of the acquisition and allocation of energy by individuals to support maintenance, activity, growth and reproduction  or thermThe first comprehensive review of marine mammal bioenergetics occurred at the Mammals in the Seas conference organized by the United Nations Food and Agriculture Organization in 1976 , feedingDespite recent advances, the field is still hindered by many of the same uncertainties and data deficiencies that existed nearly four decades ago, especially for cetaceans. As it is not feasible to address these deficiencies for all 127 extant marine mammal species, research priorities must be identified based on the perceived needs of the bioenergetics community. To achieve this, increased communication within the bioenergetic community is needed to align data needs and data generation. Our aim was to identify ‘key’ outstanding questions in the field of marine mammal bioenergetics. The intent is to stimulate and focus research that will most effectively lead to an increased understanding of the ecology and population biology of marine mammals, ultimately facilitating conservation and management efforts. This effort was conducted in tandem with a bioenergetics workshop to discuss and review the current state of knowledge on marine mammal bioenergetics.We invited 62 scientists with experience in marine mammal physiology, bioenergetics, trophic ecology and population dynamics, to identify unanswered questions in marine mammal bioenergetics. The participant list was generated by the workshop organizers with additional suggestions from invited participants. Identification of participants by workshop organizers was based on personal knowledge of participants’ research and queries of the relevant bioenergetic and marine mammal literature. Participants were asked to submit no more than 10 questions each with the following guidelines. Questions (i) could not be answered with a simple ‘yes’, ‘no’ or ‘depends’; (ii) could be related to any aspect of bioenergetics but should be applicable to methods used in marine mammal management and conservation; (iii) could be unanswerable or infeasible given current methods; and (iv) could be either species-specific or broadly relevant to a taxonomic group . Questions were collated and revised over email discussions and during the bioenergetic workshop . QuestioThe final list of questions was circulated for voting to the original 62 survey invitees and 20 additional individuals identified by the co-authors of this paper during the process. Participants voted for no more than 15 questions each, with the guidance that a question need not be applicable to all marine mammals . Voting occurred virtually via a Google Forms survey (25 August–27 September 2021). Survey participants were also asked to provide information on their expertise in marine mammal physiology and whether they had experience developing bioenergetic models . This was to help inform whether any key questions were deemed important by individuals with greater expertise in one discipline over the other (physiologists vs. bioenergetic modellers).A total of 284 initial questions were submitted by 37 of the 62 original invited participants. They ranged from detailed physiological questions to broad overarching questions about the impacts of climate change, anthropogenic disturbance and fisheries on marine mammal populations. Questions were revised by co-authors and other bioenergetic workshop participants  such thaForty-two of the 82  invited participants voted in the final survey. Most of the voting participants had current jobs in academia (78%), followed by non-profits (7.1%), government agencies (4.8%), a combination of academia and consulting (2.4%), the private sector (2.4%) or were self-employed 2.4%; . One parThe following sections briefly describe how each question is relevant to bioenergetics and conservation efforts and highlight important data gaps. Additional information on topics covered here, such as bioenergetic models, metabolic rates, body condition and growth and reproductive energetics can be found elsewhere in this special issue  in the right place, at the right time to support individual and population energy needs? How do factors such as interannual variability, climate change, fisheries and habitat loss affect prey availability? Climate change, which is rapid in some regions, is predicted to have considerable impacts on the distribution, biomass, energy density and body size of prey species , leading to reduced weaning mass of pups  or cause direct (e.g. injuries from vessels or nets) or indirect  physical impacts that have implications for energy balance. For example, marine mammals may spend less time foraging when disturbed . Traumat of pups . Our abiTursiops truncatus) and harbour porpoise (Phocoena phocoena) indicate that FMRs of small odontocetes may align more closely with the high-energy lifestyle of otariids (Ziiphidae) and sperm whales  and baleen whales. These gaps often result in the use of general allometric equations to estimate metabolic rates in bioenergetic models (e.g. Field metabolic rates (FMRs) represent an individual’s daily energy expenditure at a given time, which underpins many of the other key questions we identified in this exercise. The costs contained within FMR comprise the majority of an individual’s energy budget , and limels e.g. . ExistinMirounga angustirostris; The amount of time an animal spends engaged in certain activities  influences its energy budget through changes in intake, expenditure or both. Climate change and habitat loss alter environmental conditions, forcing (or facilitating) species to either move into new environments or adapt to their existing ones that may be undergoing rapid changes . In addiEubalaena glacialis; Once ingested, energy is directed to a variety of processes, such as digestion, the maintenance of cellular function, production of waste products, thermoregulation, mechanical work/activity, structural growth, reproduction and storage . Energy Body condition, defined as the amount of energy reserves relative to structural size, is a physiological unit of considerable interest in conservation-focused bioenergetic studies. As the physical manifestation of energy balance, body condition provides essential information about the health of individuals and populations Williams . A univeBehavioural changes are one of the first observable responses of individuals to disturbances or environmental perturbations. The resulting impact of that behavioural change on survival and reproductive success is what drives population dynamics  by measuring changes in body size and condition of lactating females relative to the growth of their dependent calves  compare with methods that provide a more direct measure of FMR (e.g. DLW) and the level of uncertainty around estimates given the assumptions of such approaches  availability to aid in killer whale population recovery . The Office of Naval Research funded the bioenergetic workshop (N000142012392) that provided support for this work.The original submitted questions and final collated questions are included in supplemental material. There are no other data associated with this article.suppl_coac055Click here for additional data file.


The required distal margin in partial mesorectal excision (PME) is controversial. The aim of this systematic review was to determine incidence and distance of distal mesorectal spread (DMS).A systematic search was performed using PubMed, Embase and Google Scholar databases. Articles eligible for inclusion were studies reporting on the presence of distal mesorectal spread in patients with rectal cancer who underwent radical resection.Out of 2493 articles, 22 studies with a total of 1921 patients were included, of whom 340 underwent long-course neoadjuvant chemoradiotherapy (CRT). DMS was reported in 207 of 1921 (10.8%) specimens (1.2% in CRT group and 12.8% in non-CRT group), with specified distance of DMS relative to the tumor in 84 (40.6%) of the cases. Mean and median DMS were 20.2 and 20.0 mm, respectively. Distal margins of 40 mm and 30 mm would result in 10% and 32% residual tumor, respectively, which translates into 1% and 4% overall residual cancer risk given 11% incidence of DMS. The maximum reported DMS was 50 mm in 1 of 84 cases. In subgroup analysis, for T3, the mean DMS was 18.8 mm (range 8–40 mm) and 27.2 mm (range 10–40 mm) for T4 rectal cancer.DMS occurred in 11% of cases, with a maximum of 50 mm in less than 1% of the DMS cases. For PME, substantial overtreatment is present if a distal margin of 5 cm is routinely utilized. Prospective studies evaluating more limited margins based on high-quality preoperative magnetic resonance imaging and pathological assessment are required.The online version contains supplementary material available at 10.1007/s10151-022-02690-1. Heald et al. popularized the concept of total mesorectal excision (TME) as curative surgical treatment for rectal cancer . In bothPartial mesorectal excision (PME), compared to TME, is a less-extensive surgical procedure associated with less morbidity and better long-term functional outcomes. It has been shown to be associated with significantly lower anastomotic leak rates, increased restorative procedure rate, shorter median hospital stay, less long-term bowel dysfunction and better urinary and sexual function –9. CurreIt is important to have a distal mesorectal margin because of the potential presence of distal mesorectal spread (DMS) of the primary rectal cancer, presenting as mesorectal lymph-node metastases, as vascular or perineural invasion or as tumor deposits. The prevalence and extent of DMS are largely unknown, but these data are prerequisites to define a safe distal resection margin. If oncologically safe, preserving as much as (meso)rectum as possible is preferred for better short-term and long-term functional outcomes –9, 12.The aim of this study was to review the reported pattern  of tumor cells in the mesorectum as a step toward reaching consensus about the distal resection margin for patients with rectal cancer undergoing PME.This systematic review was reported in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist (PRISMA) and A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 was used as a critical appraisal tool , 14. Thist 2019) was also used to look for additional references, using the anonymous mode. References of included studies were checked for other eligible studies.Systematic searches were performed from inception in PubMed (up to October 7th 2019) and Embase.com (up to October 16th 2019) with the assistance of a medical information specialist. The full search strategies for both databases are provided in Table Studies eligible for inclusion were studied reporting on the presence of malignant cells in the mesorectum in any form in patients with rectal cancer who underwent radical resection. Studies were excluded if they reported solely the intramural spread of rectal cancer, if they on lateral lymph-node metastases instead of mesorectal spread and if they did not describe the localisation of the mesorectal spread in relation to the primary tumor. Reviews or narrative studies, comment letters or non-human studies were also excluded. In case of studies with suspected overlap of patients, the most recent study was included.www.rayyan.ai) [After removal of duplicates, two reviewers (AG and SvO) independently selected the articles by screening on title and abstract using Rayyan QCRI (yyan.ai) . DiscrepThe Agency for Healthcare Research and Quality (AHRQ) recommends 11 items to assess methodological quality of cross-sectional studies , 17. ThaPrimary outcome was the distance of tumor cells in the mesorectum distal from the rectal tumor. All kinds of malignant spread in the mesorectum, in form of lymph nodes, tumor deposits, direct invasion or lymphatic permeation and extramural vascular invasion (EMVI), were extracted. The participants with DMS were classified in different subgroups depending on characteristics of the primary rectal cancer and whether or not long-course neoadjuvant chemoradiotherapy (CRT) was given. We intended to provide the DMS for every clinical distinct subgroup of rectal cancer based on, for example, TNM stage and tumor height. Low rectal cancer was defined as the lower edge of the tumor < 7 cm from the anal verge and high rectal cancer as a distance of ≥ 7 cm from the anal verge.Data analysis was performed using IBM SPSS Statistics 26. The mean and maximum DMS were calculated and displayed in tables and figures. The mean DMS was calculated only from patients where the distance of the DMS relative to the tumor was reported, so the primary data of the articles were used to calculate the means. In addition, two scatter plots were constructed to illustrate the distribution of DMS per subgroup of rectal cancer.The literature search yielded 2493 records that resulted in 1533 unique articles after removal of duplicates. Thirteen studies were identified by crosschecking references of the included articles. After screening on title and abstract, 94 articles were assessed by full text. A total of 72 articles were excluded by reasons outlined in Fig. The quality assessment is shown in Supplementary Table 1. The AHRQ scores ranged from 0 to 7. Thirteen of the included studies were considered to be of low quality (0–4) , 107–109DMS was found in 207 of the total of 1921 examined specimens (10.8%). In 84 of 207 cases, the distance of the DMS relative to the tumor was reported. The maximum reported DMS was 50 mm, which was found in one of the evaluable 84 specimens .The overall median DMS was 20.0 mm and the overall mean DMS was 20.2 mm. DMS less than 10 mm was reported in 8.3% of the examined specimens, DMS from 10 till 20 mm was reported in 38.1% of the cases, DMS from 20 till 30 mm was reported in 21.4%, DMS from 30 till 40 was reported in 22.6%, and more than 40 mm DMS was reported in 9.5% of the 84 cases . The mean DMS in the low rectal cancer group was 18.5 mm with a range of 8–30 mm.The mean DMS of the high located T3 and T4 rectal tumors was 23.4 mm (range: 10–40 mm). The mean DMS for the T3 and T4 tumors localized low was 18.4 mm with a range of 8–30 mm.Type of DMS was reported in 77 cases. In the vast majority of the cases, DMS comprised a lymph-node metastasis, namely in 65 of the 77 cases (84.4%). The mean DMS in this subgroup was 20.9 mm, with a range of 8–40 mm. In 8 cases, the spread was a tumor deposit (10.3%) with a DMS between 20 and 38 mm, in two cases, there was direct invasion distal to the mesorectum (2.6%) with a DMS of 6 and 10 mm, respectively, in one case, there was lymphatic invasion (1.3%) with a DMS of 8 mm, and in the remaining case, there was both direct invasion and a lymph-node distal in the mesorectum (1.3%) with a DMS of 10 mm.To the best of our knowledge, this is the first report that has systematically reviewed the published data about DMS in rectal cancer. The incidence was 10.8%, whereas the mean reported DMS was 20.2 mm. Using a distal margin of 30 mm would have resulted in residual tumor in 32% of cases with DMS and 10% of the patients with a distal margin of 40 mm would have had residual tumor. The maximum DMS was 50 mm. However, this was only recorded in less than 1% of the specimens with DMS . The available data suggested that DMS increased with higher T-stage. These data imply that a PME can be safely executed if a distal margin of at least 50 mm can be obtained for T3 and T4 tumors, indicating that TME should be performed for tumors located up to 5 cm proximal from the most distal part of the mesorectum as measured on preoperative MRI, see Fig. Tailoring the distal margin based on stage of disease and neoadjuvant treatment has the potential to increase the chance of tumor free distal mesorectal margins, potentially improving functional outcomes. Reducing the distal margin to 1 cm has a risk of residual DMS of 11%, which translates to an absolute risk of 1% given the fact that DMS is only found in 11% of the patients overall in this systematic review. If a distal margin of 2 cm is aimed for, a 32% risk of residual DMS results in an absolute increase of 4% for the whole group. For patients with non-locally advanced disease (T1-3a), these risks may be acceptable, given the balance between oncological safety and functional outcome. It is important to highlight that the data are not robust enough to allow firm conclusions regarding tailoring to specific patients groups, since the DMS is poorly reported.Neoadjuvant CRT has been shown to decrease the number of (positive) lymph nodes available for pathologic assessment , 113. OnSeveral studies have reported distal intramural spread in 5% of TME specimens, and this rarely exceeds 1 cm , 84, 110The current review shows that DMS beyond 2 cm can occur in a proportion of patients. Individual studies showed DMS in 0–30% of patients with rectal cancer , 105, wiOncological safety and morbidity may be inversely related when it comes to the treatment of rectal cancer. On the one hand, morbidity should be kept as low as possible. On the other hand, treatment should be oncologically safe with the lowest chance of LR. Several centers have reported similar LR rates when TME is compared to PME with a 5 cm distal mesorectal resection margin (excluding patients receiving neoadjuvant therapy) , 116–118A good quality of mesorectal excision is not only about the distal mesorectal resection margin. Some studies suggest that the integrity of the surgical plane is more important. Jiménez-Toscano et al. recently found no significant difference in local-recurrence-free survival, DFS and OS between patients with ≤ 10 mm, 11–20 mm, 21–30 mm or ≥ 31 mm distal mesorectal resection margin . In agreThis systematic review has several limitations. First, there are paucity of data in the literature and this combined with the heterogeneity and lack of detail in the existing data in terms of T-stage and neoadjuvant therapy use limits the strength of the conclusions that can be drawn. In particular, DMS is not always included in datasets as an outcome, since routine pathologic examination of the entire mesorectal specimen for individual tumor cells is not standard practice. This could explain why DMS was found in only approximately 11% of the specimens. Second, postoperative MRI data from Bondeven et al. found residual mesorectum in many cases where a formal TME was intended, potentially resulting in underreporting of DMS , 128. A These limitations mean that definite indications about the distal mesorectal resection margin should be in PME, and when a PME is safe or when a TME should be performed, it is not possible. Clearly, there is a need for a properly designed and quality controlled  study to prospectively evaluate the incidence of distal mesorectal tumor spread by precise pathologic assessment, with and without neoadjuvant treatment. This could be combined with a modified Delphi study to determine a core outcome set for pathology and MRI. In the meantime, we recommend a detailed assessment of the preoperative MRI taking into account individual variability in anatomy of the distal mesorectum, combined with a discussion of the balance between oncological safety and functional outcome with the patient, to guide the decision on the level of mesorectal transection in rectal cancer.This systematic review shows that PME is a safe procedure in those patients where a margin of 5 cm can be obtained. The data revealed an incidence of DMS in rectal cancer of 11% overall, which was 1% and 13% with and without long-course neoadjuvant CRT. The maximum reported DMS was 50 mm based on a single case, with a risk of residual DMS of 1% using a 40 mm distal margin and this risk increases to 4% with a 30 mm distal margin. Prospective studies evaluating margins based on high-quality preoperative MRI and pathological assessment are required.Scatter plot with the individual patients with distal mesorectal spread (DMS) per T-stage.Supplementary file1 Scatter plot with the individual patients with distal mesorectal spread (DMS) per T-stage (JPG 40 KB)The mean and maximum distal mesorectal spread (DMS) per level of rectal tumorSupplementary file2 The mean and maximum distal mesorectal spread (DMS) per level of rectal tumor (JPG 61 KB)Scatter plot with the individual patients with distal mesorectal spread (DMS) per level of rectal tumor.Supplementary file3 Scatter plot with the individual patients with distal mesorectal spread (DMS) per level of rectal tumor (JPG 54 KB)Supplementary file4 (DOCX 22 KB)Below is the link to the electronic supplementary material.


Meanwhile, the facile triboelectric sensor made of two annular aluminum electrodes enables the interaction interface to rapidly recognize the multidirectional finger movements. By leveraging the resonant frequency changes of the humidity sensor and output voltage waveforms of the triboelectric sensor, the proposed interaction interface is successfully demonstrated as a game control interface to manipulate a car in virtual reality (VR) space and a password input interface to enter high‐security 3D passwords, indicating its great potential in diversified applications in the future Metaverse.Current noncontact human–machine interfaces (HMIs) either suffer from high power consumption, complex signal processing circuits, and algorithms, or cannot support multidimensional interaction. Here, a minimalist, low‐power, and multimodal noncontact interaction interface is realized by fusing the complementary information obtained from a microelectromechanical system (MEMS) humidity sensor and a triboelectric sensor. The humidity sensor composed of a two‐port aluminum nitride (AlN) bulk wave resonator operating in its length extensional mode and a layer of graphene oxide (GO) film with uniform and controllable thickness, possesses an ultra‐tiny form factor  humidity sensor and a triboelectric sensor, a minimalist noncontact interaction interface with both steady and dynamic responses to finger movements is realized for high‐dimensional interactions. With the capability of detecting multimodal sensory information, the interaction interface is successfully demonstrated as a game control interface and a 3D password input interface. Thereinto, wearable HMIs are the most widely investigated domain technologies due to their unique intuitive, portable, compact, conformal, and low‐cost features .The rise of the Metaverse concept has further increased the demand for various sensory and interactive systems to perform information exchange and mutual interactions between the real world and the virtual world, such as those that can monitor natural environmental factors, human biological and physical signals, and project such information into the virtual environment for a more intuitive, immersive, and real experience.2, 3 These MEMS sensors are able to be integrated into various wearable equipment or with other wearable sensors, exhibiting good integration compatibility, low power consumption, and negligible effect on the flexible and stretchable properties of wearable HMIs. On the other hand, wearable HMIs can be directly fabricated from intrinsically flexible or stretchable materials, e.g., electronic skin, electronic‐textile, wearable patch, etc. To achieve the sensory and interactive functionality, they can be developed based on the sensing mechanisms of piezoresistive, capacitive, piezoelectric, and triboelectric effects. By contrast, the triboelectric and piezoelectric sensors are highly promising for wearable HMIs because of their self‐powered capability, especially when an enormous number of HMIs are required in the Metaverse era. Since the first invention in 2012, triboelectric nanogenerators (TENGs) based on the coupling of contact electrification and electrostatic induction and Maxwell's displacement current, have attracted worldwide interest and been investigated for diverse applications ranging from energy harvesting, self‐powered sensing, to human–machine interactions. Due to the simple configuration, low cost, wide material selection, high scalability, and good compatibility, some studies have combined the triboelectric mechanism with the piezoelectric mechanism to form hybridized HMIs, with enhanced signal multimodality and endowed multifunctionalities.To realize wearable HMIs, two general directions have been widely investigated by researchers to bridge conventional electronics with soft human skins. On the one hand, the traditionally rigid electronics can be miniaturized as tiny islands and integrated on flexible substrates, with stretchable interconnects. In the past few decades, by leveraging the wafer‐level and low‐cost micromachining processes, microelectromechanical system (MEMS) sensors such as inertial and pressure sensors have achieved a huge commercial success.12 The However, these sensors suffer from the drawbacks of high power consumption as well as complex signal processing circuits and detecting algorithms. A potential candidate to address these issues in noncontact HMIs is the triboelectric sensors with the significant advantages of self‐powered capability and facile configuration. The noncontact interaction is achieved through the electrostatic induction between triboelectric sensing elements and charged objects at a remote distance. In this regard, human fingers are ideal for such interactions since they naturally carried with charges after frequent contact with other surfaces during various daily activities. Nevertheless, the fly in the ointment is that the signals from triboelectric sensors are instantaneous and cannot support steady and continuous noncontact response, greatly hindering their applications in certain scenarios. Meanwhile, they normally require a large number of sensing electrodes to achieve multidirectional sensing, which degrades their scalability and integration capability.In addition to wearability, noncontact sensing capability is also another desired feature for the next‐generation HMIs. Recently, we have witnessed a growing interest in wearable HMIs with noncontact attributes, especially during the current pandemic. The noncontact operation of HMIs can effectively reduce the spread of viruses and improve the user experience. Current solutions for realizing noncontact wearable HMIs include optical, radar and ultrasound sensors that can remotely detect human finger motions.48 How especially those nanomaterials‐based humidity sensors. When the water molecules diffused from the surface of an approaching finger are adsorbed by the sensing materials coated on a humidity sensor, the sensor's resistance, capacitance, or resonant frequency will change in response to the approaching of the finger. Meanwhile, the response of the humidity sensor is continuous during the entire process of finger movement, which provides the possibility for noncontact HMIs with steady and continuous responses. Amongst various humidity sensors, MEMS piezoelectric resonant humidity sensors possess the advantages of high sensitivity, high resolution, and wide sensing range with the aid of their surface humidity sensing materials. Moreover, their miniaturized size, low power consumption, digital frequency output, and easy integration make them suitable for use in wearable noncontact HMIs. Whereas, humidity sensor based noncontact HMIs are not ideal for instantaneous finger motion sensing such as finger sliding direction and velocity. Normally a large humidity sensor array is required, which inevitably increases the system complexity and reduces the integration compatibility with other wearable devices. In this regard, multimodality sensor fusion could be a more promising way to achieve simultaneous steady and instantaneous sensing capabilities, compared to the construction of complex and redundant sensor arrays.On the other hand, another promising candidate to overcome these issues is the high‐performance humidity sensors, which have the capability to keenly sense the humidity changes brought by the proximity of human fingers,55 espFigureHerein, by using the complementary sensing capability of the MEMS humidity sensors and the triboelectric sensors, we propose a minimalist and multimodal noncontact interaction interface that can detect steady and instantaneous finger motions simultaneously. The noncontact interaction interface is based on the information fusion of a single MEMS piezoelectric resonant humidity sensor and a facile triboelectric sensor Figure1a. With2Q), higher stability, better power handling ability, and lower detection limit, making them more suitable as the sensing platforms. Common piezoelectric bulk wave resonators are mainly composed of a piezoelectric layer, two electrode layers (the piezoelectric layer is sandwiched between the top and bottom electrodes), and a structure layer, as shown in the inset of Figure Figure2. Different from the single top electrode design of the one‐port resonator, the top electrode of the two‐port resonator was divided into two parts, to reduce the influence of the feedthrough capacitance between resonator signal input and output terminals on the sensor signal strength. The specific mechanism can be illustrated by equivalent circuit diagrams and the electric field (Efield) distribution of the resonators shown in Figure Rm), inductance (Lm) and capacitance (Cm) in the equivalent circuit are associated with the damping, inertia and compliance of the resonator in the mechanical system, respectively. In addition, the capacitance (C0) represents the intrinsic capacitance (feedthrough capacitance) between the signal input and output terminals, which largely attenuates the signal strength of the resonator. For the one‐port resonator, the value of C0 is relatively large, because the top and bottom electrodes arranged in parallel act as the signal input and output terminals, as indicated in Figure Piezoelectric resonators are the key components that determine the performance of piezoelectric resonant humidity sensors. Compared with other types of piezoelectric resonators, such as SAW resonators, quartz QCMs, and cantilever resonators, bulk wave resonators operating in extensional vibration modes have a more compact size, higher quality factor latforms.64 Com64 ComQ To achieve a reproducible performance of the humidity sensors, vacuum filtration was adopted to prepare the GO film with uniform and controllable thickness, in which anodic aluminum oxide (AAO) membrane with large porosity was used as the filter membrane  at the resonant frequency of 10.5 MHz was distinctly higher than that of the one‐port resonator (Q = 811.5), which was beneficial to improve the stability of the humidity sensor during the test.Excited by an external signal, both resonators could generate extensional vibrations along their length direction, as indicated by the COMSOL simulation results shown in Figure 68 To –1 when the humidity changed from 10% to 90%RH. Additionally, no significant signal strength attenuation was observed throughout the test, and the high humidity sensing performance of the sensor was highly repeatable  of the flexible mode affected the stability of the test signal and increased the signal noise level, which is verified by the test results in Figure In addition to the length extensional mode, the flexible mode was another type of vibration mode that can be excited in the two‐port resonant humidity sensor as depicted in Figure 71 Nev3FigureThe dynamic response of the two‐port resonant humidity sensor operating in length extensional mode was then investigated by continuously changing the ambient humidity. For noncontact human–machine interaction, the actual response of the humidity sensors to the humidity changes brought about by the proximity of human fingers is crucial. Figure 4Through the GO‐coated MEMS piezoelectric bulk wave resonator, humidity sensing and noncontact finger interaction were achieved for various monitoring and remote‐control applications. Yet due to the demand for high‐dimensional control, while keeping the interaction interface system lean, a complementary noncontact method was desired to be integrated for more practical and real‐time functionality. Herein, we designed a facile triboelectric sensor with minimalist two annular electrodes and the same noncontact characteristics to enable multidirectional finger motion sensing. On one hand, the triboelectric sensor was able to capture the remote finger motions instantly, facilitating the rapid detection of multidirectional and dynamic finger interactions. On the other hand, the humidity sensor with a steady monitoring ability could be used for detecting the continuous operations of the finger, which was difficult to be achieved only with triboelectric sensors. Thus, with an integrated triboelectric sensor, the resultant interface was able to achieve not only steady and dynamic motion sensing, but also higher‐dimensional signals for more complex controls and interactions.FigureThe proposed triboelectric sensor was constructed with a facile configuration, consisting of only a patterned electrode layer and an interactive Ecoflex ring attached to the fingertip (the Ecoflex ring was only needed in high humidity areas like Singapore). The layout of the patterned electrode is shown in Generally speaking, when the finger slid across single‐electrode patterns (direction 1/1' and 2/2“), outputs were only generated on the respective electrode. If the finger slid across the double‐electrode patterns (direction 3/3” and 4/4“), outputs were generated on both electrodes, with the signal sequence depending on the sliding sequence. Therefore, with different sliding directions, distinguishable output waveforms were produced on E1 and E2 instantly, as depicted in Figure 5With the complementary characteristics and functionalities, the MEMS humidity sensor and triboelectric sensor were integrated with data acquisition modules, a microcontroller unit and a laptop, forming a multimodal sensory and control system for various practical applications. Enabled by the technology fusion of MEMS and TENG, the integrated interaction interface was able to contactless capture multimodal sensory information, including both the dynamic finger motion and the steady finger humidity, for rapid and continuous interactions respectively.FigureTo show the actual capability of the integrated system, car control in virtual reality (VR) space was demonstrated using defined finger interactions. As indicated in −1 (resonant frequency > 10.48 MHz), 30 km h−1 (10.47 MHz < resonant frequency ≤ 10.48 MHz), 60 km h−1 (10.46 MHz < resonant frequency ≤ 10.47 MHz), and 90 km h−1 (resonant frequency ≤10.46 MHz). The moving speed variation and car moving screenshots can be observed in Figure −1, respectively, and when the resonant frequency was higher than 10.48 MHz, the speed of the car returned to 0 km h−1. The demonstration of car control can be found in Video The generated output signals from finger interactions are plotted in Figure 6FigureExcept for the gaming control application, the proposed interaction interface can also realize noncontact 3D password input in a login system. 7In summary, we designed and integrated a humidity sensor and a triboelectric sensor to develop a minimalist, multimodal noncontact interaction interface for various multidimensional control applications. The humidity sensor was designed to recognize continuous and steady command signals during noncontact interactions, while the triboelectric sensor was intended for the identification of fast and instantaneous signals. With the advanced two‐port resonant design and uniform GO film coating, the MEMS humidity sensor successfully achieved high sensitivity, low signal noise, excellent repeatability, and rapid response and recovery speed over a wide humidity range. Benefited by these characteristics, the humidity sensor can be applied for monitoring continuous finger interactions based on different finger‐to‐sensor distances and finger dwell time. On this basis, the triboelectric sensor with a facile two‐electrode design was then integrated with the humidity sensor to realize the complementary monitoring of multidirectional and dynamic finger movements. With this unique complementary information fusion, the proposed noncontact interaction interface was able to provide multimodal continuous and dynamic sensory information for various human–machine interactions with lower power consumption and simpler system structure, as compared with other noncontact HMIs (Table 8The fabrication of the piezoelectric resonators started with an n‐type silicon‐on‐insulator (SOI) wafer  was diluted to 0.02 wt% using deionized (DI) water. Then, 1 mL of the diluted GO dispersion was transferred to the Buchner funnel of the vacuum filtration set up with a pipette. The Buchner funnel was pre‐filled with 150 mL of DI water, and an anodic aluminum oxide (AAO) membrane (Whatman 6809‐5002) was placed below as a filter membrane. After the water in the Buchner funnel was vacuumed out, a uniform GO film attached to the AAO film was obtained. Subsequently, the GO film together with the AAO membrane was placed on the surface of DI water. Under the action of the water surface tension, the GO film gradually separated from the AAO membrane and continued to float on the water surface. Finally, the piezoelectric resonator was immersed in the DI water and lifted up from the bottom of the GO film to complete the GO film transfer.2 flow rates. Meanwhile, the outlet of the chamber was connected to a commercial hygrothermograph (AZ8721) to calibrate the humidity and temperature inside the chamber. The humidity response of the sensor was detected and recorded by a network analyzer (R&S ZNB20) and a PC with an installed LabVIEW program.During the humidity response characterization, the humidity sensor was fixed in a metallic chamber  was poured into a 3D printed mold, solidified to form a belt, and then taken out and fixed into a ring shape with glue  to characterize the sensor's noncontact interaction performance. While during the application demonstrations, the output voltage waveforms were recognized by a programmable Arduino UNO and converted into corresponding control commandsThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.Supplemental Video 1Click here for additional data file.Supplemental Video 2Click here for additional data file.Supplemental Video 3Click here for additional data file.Supplemental Video 4Click here for additional data file.Supplemental Video 5Click here for additional data file.