bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cold‐sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature
Authors: Reimúndez Alfonso , Fernández‐Peña Carlos , Ordás Purificación , Hernández‐Ortego Pablo , Gallego Rosalía , Morenilla‐Palao Cruz , Navarro Juan , Martín‐Cora Francisco , Pardo‐Vázquez José Luís , Schwarz Lindsay A. , Arce Victor , Viana Félix , Señarís Rosa 
Published: October 2022

AbstractAimPhysiological functions in mammals show circadian oscillations, synchronized by daily cycles of light and temperature. Central and peripheral clocks participate in this regulation. Since the ion channel TRPM8 is a critical cold sensor, we investigated its role in circadian function.MethodsWe used TRPM8 reporter mouse lines and TRPM8‐deficient mice. mRNA levels were determined by in situ hybridization or RT‐qPCR and protein levels by immunofluorescence. A telemetry system was used to measure core body temperature (Tc).ResultsTRPM8 is expressed in the retina, specifically in cholinergic amacrine interneurons and in a subset of melanopsin‐positive ganglion cells which project to the central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. TRPM8‐positive fibres were also found innervating choroid and ciliary body vasculature, with a putative function in intraocular temperature, as shown in TRPM8‐deficient mice. Interestingly, Trpm8−/− animals displayed increased expression of the clock gene Per2 and vasopressin (AVP) in the SCN, suggesting a regulatory role of TRPM8 on the central oscillator. Since SCN AVP neurons control body temperature, we studied Tc in driven and free‐running conditions. TRPM8‐deficiency increased the amplitude of Tc oscillations and, under dim constant light, induced a greater phase delay and instability of Tc rhythmicity. Finally, TRPM8‐positive fibres innervate peripheral organs, like liver and white adipose tissue. Notably, Trpm8−/− mice displayed a dysregulated expression of Per2 mRNA in these metabolic tissues.ConclusionOur findings support a function of TRPM8 as a temperature sensor involved in the regulation of central and peripheral clocks and the circadian control of Tc.
Robot‐assisted laparoscopic surgery with a fluorescent near‐infrared ray ureteral catheter for a rectal cancer patient with pelvic kidney: A case report
Authors: Hasegawa Noboru , Takeyama Hiroshi , Suzuki Yozo , Noura Shingo , Ikenaga Masakazu , Odagiri Kazuki , Yanagimoto Yoshitomo , Yamashita Masafumi , Shimizu Junzo , Kawase Tomono , Imamura Hiroshi , Iwazawa Takashi , Tomita Naohiro , Dono Keizo 
Published: October 2022

AbstractAn 85‐year‐old woman presented with a stomachache after a meal and was admitted to the previous clinic. Multi‐detector computed tomography (CT) of the abdomen showed wall thickening in the rectum and right ectopic pelvic kidney. Colonoscopy revealed a mass at the rectum, and a biopsy showed adenocarcinoma. CT showed no lymphadenopathy or distant metastasis. Hartmann's procedure with fluorescent near‐infrared ray ureteral catheters was used to avoid causing urinary injury. Robotic surgery was performed while checking the route of the ureter in near‐infrared mode. The patient was discharged on postoperative day 14 without specific complications. This case appears to be the first of robot‐assisted laparoscopic surgery for a rectal cancer patient with pelvic kidney.
Immunopathology of terminal complement activation and complement C5 blockade creating a pro‐survival and organ‐protective phenotype in trauma
Authors: Yang Zhangsheng , Nunn Miles A. , Le Tuan D. , Simovic Milomir O. , Edsall Peter R. , Liu Bin , Barr Johnny L. , Lund Brian J. , Hill‐Pryor Crystal D. , Pusateri Anthony E. , Cancio Leopoldo C. , Li Yansong 
Published: October 2022

Background and PurposeTraumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo.Experimental ApproachComplement activation products and cytokines were analysed in plasma from 54 combat casualties. The correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed. Nomacopan was administered to rats subjected to lethal TH (blast injury and haemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiological parameters, and laboratory profiles.Key ResultsEarly TCA was associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with the severity of tissue damage and mortality. The addition of nomacopan to a damage‐control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved haemodynamics and metabolism, attenuated tissue and organ damage, and increased survival.Conclusion and ImplicationsPrevious findings of our and other groups revealed that early TCA represents a rational therapeutic target for trauma patients. Nomacopan as a pro‐survival and organ‐protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities.
Prostaglandin EP3 receptor activation is antinociceptive in sensory neurons via PI3Kγ, AMPK and GRK2
Authors: König Christian , Ebersberger Andrea , Eitner Annett , Wetzker Reinhard , Schaible Hans‐Georg 
Published: October 2022

Background and PurposeProstaglandin E2 is considered a major mediator of inflammatory pain, by acting on neuronal Gs protein‐coupled EP2 and EP4 receptors. However, the neuronal EP3 receptor, colocalized with EP2 and EP4 receptor, is Gi protein‐coupled and antagonizes the pronociceptive prostaglandin E2 effect. Here, we investigated the cellular signalling mechanisms by which the EP3 receptor reduces EP2 and EP4 receptor‐evoked pronociceptive effects in sensory neurons.Experimental ApproachExperiments were performed on isolated and cultured dorsal root ganglion (DRG) neurons from wild type, phosphoinositide 3‐kinase γ (PI3Kγ)−/−, and PI3Kγkinase dead (KD)/KD mice. For subtype‐specific stimulations, we used specific EP2, EP3, and EP4 receptor agonists from ONO Pharmaceuticals. As a functional readout, we recorded TTX‐resistant sodium currents in patch‐clamp experiments. Western blots were used to investigate the activation of intracellular signalling pathways. EP4 receptor internalization was measured using immunocytochemistry.Key ResultsDifferent pathways mediate the inhibition of EP2 and EP4 receptor‐dependent pronociceptive effects by EP3 receptor stimulation. Inhibition of EP2 receptor‐evoked pronociceptive effect critically depends on the kinase‐independent function of the signalling protein PI3Kγ, and adenosine monophosphate activated protein kinase (AMPK) is involved. By contrast, inhibition of EP4 receptor‐evoked pronociceptive effect is independent on PI3Kγ and mediated through activation of G protein‐coupled receptor kinase 2 (GRK2), which enhances the internalization of the EP4 receptor after ligand binding.Conclusion and ImplicationsActivation of neuronal PI3Kγ, AMPK, and GRK2 by EP3 receptor activation limits cAMP‐dependent pain generation by prostaglandin E2. These new insights hold the potential for a novel approach in pain therapy.
Shaking and splashing—A case study of far‐field effects of the Mjølnir asteroid impact on depositional environments in the Barents Sea
Authors: Bruhn Rikke , Nagy Jenő , Smelror Morten , Dypvik Henning , Glimsdal Sylfest , Pegrum Richard , Cavalli Carlo 
Published: October 2022

AbstractThe Mjølnir impact crater in the Norwegian Barents Sea features among the 20 largest impact craters listed in the Earth Impact Database. The impact is dated to 142 ± 2.6 Ma, corresponding closely to the Jurassic/Cretaceous boundary in the Boreal stratigraphy. Multidisciplinary studies carried out over the last three decades have suggested that the up to 40 km wide crater was created by a 1–3 km diameter impactor colliding with a shallow epicontinental sea, causing regional havoc and a regional ecological crisis that followed in its wake. Only minor evidence for the consequences of the impact for the surrounding depositional basins has been documented so far. This study describes a large submarine slump penetrated by hydrocarbon exploration well 7121/9‐1, located in the southern Hammerfest Basin and approximately 350 km away from the impact site. The slump is dated by a black shale drape, which contains characteristic impact‐related biotic assemblages and potential ejecta material. This precise dating enables us to associate the slump with large‐scale fault movements and footwall collapse along the basin‐bounding Troms‐Finnmark Fault Complex, which we conclude were caused by shock waves from the Mjølnir impact and the passage of associated tsunami trains. The draping black shale is interpreted to represent significant reworking of material from the contemporary seabed by tsunamis and currents set up by the impact.
Are there more women in the dentist workforce? Using an intersectionality lens to explore the feminization of the dentist workforce in the UK and US
Authors: Fleming Eleanor , Neville Patricia , Muirhead Vanessa Elaine 
Published: October 2022

AbstractIn this paper, we seek to understand feminization of the dentist workforce moving beyond previous research that has looked at gender in isolation. We contend that little consideration has been given to how gender interacts with other important social identities such as race/ethnicity to influence the opportunities and barriers that female dentists encounter during their dental career. We argue that the scholarly debate about the feminization of the dentistry has not acknowledged the intersectionality of women's lives. Intersectionality describes how multiple social identities (such as race/ethnicity, gender, and class) overlap and interact to inform outcomes, creating disadvantages and/or privileges. Our thesis is that the increasing feminization of the dentist workforce is complicated and paradoxical, creating both opportunities for women and gender imbalances and blockages within the profession. To support our thesis, we critically reviewed the literature on feminization and analysed UK and US workforce data. While the female dentist workforce in both the UK and the US has increased significantly over the past decade, the growth in the number of female dentists was not equal across all racial/ethnic groups. The largest increase in the number of female dentists was among White and Asian women. Viewing the feminization of the dentist workforce through an intersectionality lens exposes the multiple and complex experiences of women, as well as the power dynamics in dentistry. Feminization in dentistry demonstrates the importance of presence, privilege, and power. Based on our assessment of the dentist workforce, dentistry may be less inclusive, despite being perceived as more diverse. Further research should explore how power and privilege may operate in dentistry. Dentistry should embrace intersectionality to provide an inclusive evaluation of equity in the workforce.
Effects of diabetes/hyperglycemia on peri‐implant biomarkers and clinical and radiographic outcomes in patients with dental implant restorations: A systematic review and meta‐analysis
Authors: Lv Xiaolei , Zou Lilin , Zhang Xiaomeng , Zhang Xin , Lai Hongchang , Shi Junyu 
Published: October 2022

AbstractObjectiveThe objective of this study is to systematically analyze the effects of diabetes mellitus/hyperglycemia (DM/HG) on peri‐implant biomarkers and clinical and radiographic outcomes in patients undergoing implant treatment.Materials and MethodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched up to March 2022. Studies reporting on peri‐implant biomarkers, and clinical and radiographic outcomes in patients with different glycemic status levels (HbA1c) were included. Several analyses were conducted, such as meta‐analysis, sensitivity analysis, dose–response meta‐analysis (DRMA), and robust error meta‐regression (REMR).ResultsA total of 10 studies and 634 participants were included for analysis, with a maximum follow‐up of six years in function. The level of advanced glycation end products (AGEs) in peri‐implant crevicular fluid (PICF) was significantly higher in the DM/HG group than in the healthy group (p < .01). Subgroup analyses showed that a set of negative regulators of bone metabolism (including IL‐6, TNF‐α, IL‐8, and RANKL) were significantly higher in the DM/HG group (p = .01). Implant survival rate (100%) was not compromised in patients with an HbA1c level less than 10%. Outcomes of implant stability quotient (ISQ) values, bleeding on probing rate (BOP%), probing depth (PD), and marginal bone loss (MBL) in the DM/HG group were significantly worse than those in the healthy group (p = .04, <0.01, 0.01, <0.01, respectively). DRMA results showed AGE accumulation in PICF, PD, and MBL worsened in a dose–response dependent manner with elevated HbA1c levels (<6%, 6–8%, >8%; p = .04, 0.02, <0.01, respectively).ConclusionsDM/HG can upregulate negative regulators of bone metabolism and compromise peri‐implant health. In addition, there are dose–response relationships between HbA1c levels and AGE accumulation in PICF, PD, and MBL.
Posterior nasal neurectomy for intractable rhinitis: A systematic review of the literature
Authors: Lee Mun Leng , Chakravarty Patrick Daragh , Ellul David 
Published: October 2022

AbstractBackgroundRhinitis affects up to 40% of the population worldwide and can significantly reduce quality of life. Some patients remain symptomatic despite maximal medical therapy. In refractory cases, posterior nasal neurectomy (PNN—the endoscopic division of the intranasal nerve branches containing postganglionic parasympathetic fibres) is postulated to reduce symptom burden.Objectives of ReviewTo establish whether PNN is effective and safe in the management of allergic and non‐allergic rhinitis.Type of ReviewSystematic review.MethodsA comprehensive literature search was undertaken using PubMed, EMBASE, MEDLINE, and Cochrane. The inclusion criteria were: studies published in English, studies where PNN was performed either with or without additional procedures, and where measures of objective/subjective outcomes and/or complications were reported. Extracted data included study type, sample size, surgical technique, study population characteristics, follow‐up period, outcome measures, complications of surgery, and symptom outcomes.ResultsA total of 23 articles satisfied the inclusion criteria studying in total 2282 patients. Sample size ranged from 8 to 1056. There were 3 randomised controlled trials, 3 case‐control studies, and the remaining 17 were case series using both objective and subjective outcome measures. All but one study found improved patient‐reported outcomes following PNN. Complications were reported in 14 studies—epistaxis was the most common complication and was observed in 30 patients (1.5% of subjects).ConclusionsPNN had a low rate of complications. Although most studies reported significant symptomatic improvement, their heterogeneity, level of evidence, study design, and/or quality was not sufficient to draw any firm conclusions on the effectiveness of the procedure. Larger, well‐designed studies are needed to clarify its role in the management of difficult‐to‐treat rhinitis.
Laryngopharyngeal symptoms and oesophageal disorder: The role of heterotopic gastric mucosa in upper oesophagus
Authors: Yu Xiaoyun , Wang Jiaqi , Jin Tian , Xiang Lizhi , Pan Xiaoli , Hou Xiaohua 
Published: October 2022

AbstractBackgroundHeterotopic gastric mucosa in the upper oesophagus (HGMUE) was considered as geneogenous manifestation. However, its clinical characteristics may be beyond our knowledge if we focus on its extra‐oesophageal presentation. So the aim of this study was to investigate the relationship between HGMUE and laryngopharyngeal symptoms.MethodEight hundred and eleven patients who had gastric endoscopy examination were enrolled in this study and the cervical oesophagus was examined for the patch during withdrawal of the endoscope. Questionnaire for gastroesophageal reflux disease (GERD‐Q) and Reflux Symptom Index (RSI) were completed by all the patients. Pathology feature and therapeutic effect of HGMUE patients were evaluated.ResultAbout 34.53% of the patients undergoing the gastroduodenoscopy had laryngopharyngeal (LP) symptoms. The relevance rate of HGMUE in LP(+) group (10.69%) was higher than that in LP(−) group (2%). The LP symptoms were related to the histological type and expression of H+‐K+‐ATPase in the histological sample of HGMUE patients. The positive rate of H+‐K+‐ATPase was 100% in LP(+) group, and that in LP(−) group was 28.6%. PPI therapy was effective for improving the LP symptoms in HGMUE patients. The RSI score in LP(+) patients decreased from 8.12 ± 1.46 at baseline to 4 ± 0.74 at the end of 8 weeks after treatment of PPI.ConclusionHGMUE was an important cause of LP symptoms in patients, especially in those who had no evidence of GERD. The mechanism of HGMUE‐induced LP symptoms was due to its location and the function of acid secretion according to the endoscopic finding and histologic characteristics.
Can You Hear Me Now? Sensitive Comparisons of Human and Machine Perception
Authors: Lepori Michael A. , Firestone Chaz 
Published: October 2022

AbstractThe rise of machine‐learning systems that process sensory input has brought with it a rise in comparisons between human and machine perception. But such comparisons face a challenge: Whereas machine perception of some stimulus can often be probed through direct and explicit measures, much of human perceptual knowledge is latent, incomplete, or unavailable for explicit report. Here, we explore how this asymmetry can cause such comparisons to misestimate the overlap in human and machine perception. As a case study, we consider human perception of adversarial speech — synthetic audio commands that are recognized as valid messages by automated speech‐recognition systems but that human listeners reportedly hear as meaningless noise. In five experiments, we adapt task designs from the human psychophysics literature to show that even when subjects cannot freely transcribe such speech commands (the previous benchmark for human understanding), they can sometimes demonstrate other forms of understanding, including discriminating adversarial speech from closely matched nonspeech (Experiments 1 and 2), finishing common phrases begun in adversarial speech (Experiments 3 and 4), and solving simple math problems posed in adversarial speech (Experiment 5) — even for stimuli previously described as unintelligible to human listeners. We recommend the adoption of such “sensitive tests” when comparing human and machine perception, and we discuss the broader consequences of such approaches for assessing the overlap between systems.
How does a CIED presence influence chances and safety of haemodialysis access? Conclusions from over 3000 thoracic venografies
Authors: Czajkowski Marek , Polewczyk Anna , Jacheć Wojciech , Nowosielecka Dorota , Tułecki Łukasz , Stefańczyk Paweł , Kutarski Andrzej 
Published: October 2022

AbstractPatients requiring temporal or permanent catheter or arterio‐venous fistula (AVF) for haemodialysis may be in challenging situation, if they are cardiovascular implantable electronic devices (CIED) carriers.Materials and MethodsThe authors analysed preoperative venogrphies of 3100 patients referred for transvenous lead extraction for a possible chance of safe haemodialysis catheter (HC) implantation or proper AVF function.ResultsA chance of safe catheter implantation parallel to existing leads reaches 68.8% ipsilaterally to CIED. Contraindications for implantation have been found in less than 2% of cases contralaterally. Ipsilaterally proper AVF function chance has been found in 50.3% of the cases and almost 98% contralaterally. A bilateral chest electrodes location require the special attention. Abandoned lead, lead burden, bilateral leads, additional lead implantation or abandonment, and implant duration may have a significant influence on HC insertion or proper function of arteriovenous fistula.Conclusion(1) Obstruction of prominent thoracic veins is a frequent finding in CIED carriers and may impede or disable implantation haemodialysis accesses. (2) Implantation of temporary or permanent HC may be questionable ipsilaterally to the CIED in 31.2% and contralaterally in 2.0% of patients. Proper function of AVF is uncertain in 49.7% ipsilaterally and 2.1% contralaterally to CIED. (3) Pacing history and leads dwell time influence chances of success haemodialysis access even on the free‐from CIED chest side. (4) Proper venous flow evaluation seems to be valuable in CIED carriers before an attempt of haemodialysis access formation, even contralaterally.
Controlled oxygenated rewarming as novel end‐ischemic therapy for cold stored liver grafts. A randomized controlled trial
Authors: Minor Thomas , von Horn Charlotte , Zlatev Hristo , Saner Fuat , Grawe Melanie , Lüer Bastian , Huessler Eva‐Maria , Kuklik Nils , Paul Andreas 
Published: October 2022

AbstractAbrupt return to normothermia has been shown a genuine factor contributing to graft dysfunction after transplantation. This study tested the concept to mitigate reperfusion injury of liver grafts by gentle warming‐up using ex vivo machine perfusion prior to reperfusion. In a single center randomized controlled study, livers were assigned to conventional static cold storage (SCS) alone or to SCS followed by 90 min of ex vivo machine perfusion including controlled oxygenated rewarming (COR) by gentle and protracted elevation of the perfusate temperature from 10°C to 20°C. Primary outcome mean peak aspartate aminotransferase (AST) was 1371 U/L (SD 2871) after SCS versus 767 U/L (SD 1157) after COR (p = 0.273). Liver function test (LiMAx) on postoperative day 1 yielded 187 μg/kg/h (SD 121) after SCS, but rose to 294 μg/kg/h (SD 106) after COR (p = 0.006). Likewise, hepatic synthesis of coagulation factor V was significantly accelerated in the COR group immediately after transplantation (103% [SD 34] vs. 66% [SD 26]; p = 0.001). Fewer severe complications (Clavien‐Dindo grade ≥3b) were reported in the COR group (8) than in the SCS group (15). Rewarming/reperfusion injury of liver grafts can be safely and effectively mitigated by controlling of the rewarming kinetics prior to blood reperfusion using end‐ischemic ex vivo machine perfusion after cold storage.