bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocyte growth factor, colony-stimulating factor 1, CD40, and 11 other inflammation-related proteins are associated with pain in diabetic neuropathy: exploration and replication serum data from the Pain in Neuropathy Study
Authors: Bäckryd Emmanuel , Themistocleous Andreas , Larsson Anders , Gordh Torsten , Rice Andrew S.C. , Tesfaye Solomon , Bennett David L. , Gerdle Björn 
Published: August 2021

Abstract
One in 5 patients with diabetes suffers from chronic pain with neuropathic characteristics, but the pathophysiological mechanisms underlying the development of neuropathic pain in patients with diabetic distal symmetrical polyneuropathy (DSP) are poorly understood. Systemic low-grade inflammation has been implicated, but there is still a considerable knowledge gap concerning its scope and meaning in this context. The aim of the study was to establish the broad inflammatory signature of painful diabetic DSP in serum samples from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the present two cohorts exploration–replication study (180 participants in each cohort), serum samples from Pain in Neuropathy Study participants were analyzed with the Olink INFLAMMATION panel (Olink Bioscience, Uppsala, Sweden) that enables the simultaneous measurement of 92 inflammation-related proteins (mainly cytokines, chemokines, and growth factors). In both the exploration and the replication cohort, we identified a high-inflammation subgroup where 14 inflammation-related proteins in particular were associated with more neuropathy and higher pain intensity. The top 3 proteins were hepatocyte growth factor, colony-stimulating factor 1, and CD40 in both cohorts. In the exploratory cohort, additional clinical data were available, showing an association of inflammation with insomnia and self-reported psychological distress. Hence, this cross-sectional exploration–replication study seems to confirm that low-grade systemic inflammation is related to the severity of neuropathy and neuropathic pain in a subgroup of patients with diabetic DSP. The pathophysiological relevance of these proteins for the development of neuropathic pain in patients with diabetic DSP must be explored in more depth in future studies.
Shared decision-making approach to taper postoperative opioids in spine surgery patients with preoperative opioid use: a randomized controlled trial
Authors: Uhrbrand Peter , Rasmussen Mikkel Mylius , Haroutounian Simon , Nikolajsen Lone 
Published: August 2021

Abstract
Persistent opioid use is common after surgery, and patients with preoperative opioid use represent a major challenge in this regard. The aim of this randomized controlled trial was to determine the effect of a personalized opioid tapering plan vs standard of care in patients with a preoperative opioid use undergoing spine surgery at Aarhus University Hospital, Denmark. Postoperative outcomes included opioid use, pain, contacts with the healthcare system, patient satisfaction, and withdrawal symptoms. Overall, 110 patients were randomized; 55 into the intervention and control groups each. Five patients (proportion = 0.09, 95% confidence interval [CI] [0.04-0.21]) in the intervention group compared with 13 patients (0.25, 95% CI [0.15-0.39]) in the control group were unable to taper opioids to their preoperative consumption 1 month after discharge (P = 0.03) (primary outcome). Likewise, more patients in the intervention group succeeded in tapering opioids to zero 3 months after discharge (37 patients; 0.71, 95% CI [0.57-0.82] vs 23 patients; 0.43, 95% CI [0.30-0.56], P = 0.003). Fewer patients in the intervention group had pain-related contacts to health care the first 2 weeks after discharge (21 patients; 0.40, 95% CI [0.28-0.54] vs 31 patients; 0.60, 95% CI [0.46-0.73], P = 0.04). There was no difference in satisfaction with pain treatment over the first 2 weeks or the incidence of withdrawal symptoms during the first month after discharge. Pain intensity was similar between both groups at all time points. These results suggest that a personalized tapering plan at discharge combined with telephone counselling 1 week after discharge assists patients in postoperative opioid tapering.
Postnatal development of inner lamina II interneurons of the rat medullary dorsal horn
Authors: Mermet-Joret Noëmie , Alba-Delgado Cristina , Descheemaeker Amelie , Gabrielli Francois , Dallel Radhouane , Antri Myriam 
Published: August 2021

Abstract
Pain processing in young mammals is immature. Despite the central role of the medullary dorsal horn (MDH) in processing orofacial sensory information, the maturation of the neurons within the MDH has been largely overlooked. Combining in vitro electrophysiological recordings and 3D morphological analysis over the first postnatal month in rats, we investigated the age-dependent development of the neurons within the inner lamina II (IIi) of the MDH. We show the lamina IIi neuronal population transition into a more hyperpolarized state, with modification of the action potential waveform, and a shift from single spiking, at early postnatal ages, to tonic firing and initial bursting at later stages. These physiological changes are associated with a strong structural remodelling of the neuronal morphology with most of the modifications occurring after the third postnatal week. Among the lamina IIi neuronal population, the subpopulation of interneurons expressing the γ isoform of the protein kinase C (PKCγ+) are key elements for the circuits underlying facial mechanical allodynia. How do they develop from the rest of the lamina IIi constitute an important question that remained to be addressed. Here, we show that PKCγ+ interneurons display electrophysiological changes over time comparable with the PKCγ− population. However, they show a distinctive increase of the soma volume and primary branches length, as opposed to the PKCγ− population. Together, our data demonstrate a novel pattern of late postnatal maturation of lamina IIi interneurons, with a spotlight on PKCγ+ interneurons, that may be relevant for the development of orofacial sensitivity.
Longitudinal Outcomes in Adolescents After Referral for Metabolic and Bariatric Surgery
Authors: Qureshi Faisal G. , Wiegand Jared G. , O'Neill Grayce , Allen Brandi , Wools Gentry , Klement Jessica , Franklin Elizabeth V. , Messiah Sarah E. , Gupta Olga T. 
Published: August 2021

ABSTRACTBackground:Metabolic and bariatric surgery (MBS) can be a well tolerated and effective treatment option for severe obesity in adolescents. We compared outcomes for adolescents that did and did not proceed to surgery.Methods:A single‐center longitudinal study (2015–2020). Patients were identified as LSG if they completed laparoscopic sleeve gastrectomy within 6 months of initial visit and NoLSG if they did not. Chi‐square, Fisher exact, nonparametric Kruskal‐Wallis tests, and Linear Mixed Models (LMM) were used to compare outcomes over 2 years.Results:Three hundred fifty‐two adolescents were referred with a mean age of 15.6 ± 1.4, 69% girls, 38% Hispanic, and 78% had noncommercial insurance. The median baseline weight was 135 kg and body mass index (BMI) was 48 kg/m2; 42% had a BMI >50. Seventy‐nine (22%) underwent LSG whereas 273 (78%) did not complete MBS primarily because of lack of interest. LSG patients had 21% total weight loss and 22% total BMI loss at 24 months whereas NoLSG patients had 4% total weight gain and 3% BMI gain (P < 0.01). Obesity‐associated conditions improved in the LSG group (P < 0.01). Follow‐up in both groups was poor (⩽30% at 24 months). Patients with public insurance and those with BMI from 50 to 59.9 kg/m2 were high performing LSG patients.Conclusions:A minority (22%) of adolescents referred for MBS proceeded to surgery, despite its demonstrated efficacy and safety in adolescence. Those that did not undergo surgery continued to gain weight. Further research is needed to understand patient preferences or concerns related to MBS utilization during adolescence.
Early Change in Fecal Calprotectin Predicts One‐Year Outcome in Children Newly Diagnosed With Ulcerative Colitis
Authors: Krishnakumar Chenthan , Ananthakrishnan Ashwin N. , Boyle Brendan M. , Griffiths Anne M. , LeLeiko Neal S. , Mack David R. , Markowitz James F. , Rosh Joel R. , Sauer Cary G. , Walters Thomas D. , Bonkowski Erin , Denson Lee A. , Hyams Jeffrey S. , Kugathasan Subra 
Published: August 2021

ABSTRACTIntroduction:While fecal calprotectin (FC) is used to assess disease activity in ulcerative colitis (UC) there are little data concerning the role of serial FC levels at diagnosis in predicting clinical course. We sought to determine whether FC at diagnosis or early change following therapy predicts clinical outcomes in pediatric UC.Methods: Children with newly diagnosed UC were treated with standardized regimens of mesalamine or corticosteroids (CS). CS tapering and escalation to additional therapy or colectomy were by protocol. Patients with baseline or week 4 or week 12 FC levels were included in the analysis. Our primary outcome was CS‐free remission on mesalamine at week 52. We compared the prognostic value of a baseline FC as well as a change in FC by week 4 or week 12 in predicting clinical outcomes.Results:The study included 352 children (113 initial mesalamine, 239 initial CS, mean age 12.6 years) with UC. At Week 52, 135 (38.3%), 84 (23.8%), and 19 (5.4%) children achieved CS‐free remission, needed anti‐tumor necrosis factor therapy or had colectomy respectively. Baseline FC was not associated with CS‐free remission at week 52. However, both week 4 (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.901.00) and week 12 FC levels (OR 0.91, 95% CI 0.87–0.96) were associated with outcomes, with the latter having a stronger association with CS‐free remission. Patients with a >75% decrease by 12 weeks, had a 3‐fold increased likelihood of CS‐free remission at 1 year.Discussion:Longitudinal changes in FC may predict 1 year outcomes better than values at diagnosis in children with a new diagnosis of UC.
Oral Manifestations of Early Syphilis in Adults: A Systematic Review of Case Reports and Series
Authors: Zhou Xiao , Wu Min-Zhi , Jiang Ting-Ting , Chen Xiang-Sheng 
Published: August 2021

Abstract
Rapid emergence of syphilis and oral sexual behaviors has focused attention on oral syphilis, and published reports of cases with oral syphilis have increased in the recent decades. We performed a systematic literature review by searching articles from PubMed, EMBSE, and Google Scholar, looking for case reports or series that would potentially have the clinical characteristics and outcomes for each individual case with oral syphilis. A total of 145 cases with the infection, from 95 studies, were identified to include in our review. Two main clinical phenotypes (ulcerative lesions and mucous patches) appeared to be of particular relevance to oral manifestations. A solitary ulcer was mostly manifested as the lesion of primary syphilis (91.7%) preferentially located on the upper lip, tongue, palate, and buccal mucosa. The most affected anatomical site in the patients with single location involved was the tongue (37.5%), followed by the lips (29.5%), palates (19.3%), and buccal mucosa (6.8%). It is concluded that oral syphilis has its predominant clinical phenotypes although it can manifest in diverse manners.
Country-level Association of Socioeconomic, Environmental and Healthcare-Related Factors with the Disease-Burden and Mortality Rate of COVID-19
Authors: Chowdhury Tasnuva , Mahbub Upal , Rahman Tauhidur 
Published: August 2021

AbstractBackgroundCOVID-19 pandemic is rapidly expanding throughout the world right now. Caused by a novel strain of the coronavirus, the manifestation of this pandemic shows a unique level of disease burden and mortality rate in different countries.ObjectiveIn this paper, we investigated the effects of several socioeconomic, environmental, and healthcare-related factors on the disease burden and mortality rate of COIVID-19 across countries. Our main objective is to provide a macro-level understanding of the most influential socioeconomic, environmental, and healthcare-related factors associated with the disease burden and mortality rate metrics without human bias.MethodsWe developed a multiple linear regression model using backward elimination to find the best fitting between reported death and cases across countries for country-level aggregated independent factors keeping COVID-19 test statistic in consideration. Notably, the method requires minimum human intervention and handles confounding effects intrinsically.ResultsOur results show that while the COVID-19 pandemic is seemingly spreading more rapidly in economically affluent countries, it Is more deadly in countries with inadequate healthcare infrastructure, lower capacity of handling epidemics, and lower allocation of the healthcare budget. We also did not find evidence of any association between environmental factors and COVID-19.ConclusionWe took the number of tests performed into account and normalized the case and mortality counts based on the cumulative distribution of cases across days. Our analysis of the standardized factors provides both the direction and relative importance of different factors leading to several compelling insights into the most influential socioeconomic and healthcare infrastructure-related factors from a country-level view.
Low risk of SARS-CoV-2 transmission via fomite, even in cold-chain
Authors: Sobolik Julia S. , Sajewski Elizabeth T. , Jaykus Lee-Ann , Cooper D. Kane , Lopman Ben A. , Kraay Alicia NM. , Ryan P. Barry , Guest Jodie L. , Webb-Girard Amy , Leon Juan S. 
Published: August 2021

SummaryBackgroundCountries continue to debate the need for decontamination of cold-chain food packaging to reduce possible SARS-CoV-2 fomite transmission among workers. While laboratory-based studies demonstrate persistence of SARS-CoV-2 on surfaces, the likelihood of fomite-mediated transmission under real-life conditions is uncertain.MethodsUsing a quantitative risk assessment model, we simulated in a frozen food packaging facility 1) SARS-CoV-2 fomite-mediated infection risks following worker exposure to contaminated plastic packaging; and 2) reductions in these risks attributed to masking, handwashing, and vaccination.FindingsIn a representative facility with no specific interventions, SARS-CoV-2 infection risk to a susceptible worker from contact with contaminated packaging was 2·8 × 10−3per 1h-period (95%CI: 6·9 × 10−6, 2·4 × 10−2). Implementation of standard infection control measures, handwashing and masks (9·4 × 10−6risk per 1h-period, 95%CI: 2·3 × 10−8, 8·1 × 10−5), substantially reduced risk (99·7%). Vaccination of the susceptible worker (two doses Pfizer/Moderna, vaccine effectiveness: 86-99%) combined with handwashing and masking reduced risk to less than 1·0 × 10−6. Simulating increased infectiousness/transmissibility of new variants (2-, 10-fold viral shedding) among a fully vaccinated workforce, handwashing and masks continued to mitigate risk (2·0 × 10−6-1·1 × 10−5risk per 1h-period). Decontamination of packaging in addition to these interventions reduced infection risks to below the 1·0 × 10−6risk threshold.InterpretationFomite-mediated SARS-CoV-2 infection risks were very low under cold-chain conditions. Handwashing and masking provide significant protection to workers, especially when paired with vaccination.FundingU.S. Department of Agriculture
Correlation between Proinflammatory cytokines and severity of COVID-19 within Palestinian Population
Authors: Basha Walid , Nazzal Zaher , El-Hamshary Yousef , Odeh Anwar , Hijjawi Lama , Doden Mahmoud , Musa Ahmad , Ruzzeh Saad 
Published: August 2021

AbstractCOVID-19 was characterized by cytokine storm and endothelial dysfunction in severely ill patients. As the severity of the infection was corelated with ethnicity, this study aimed to assess the correlation of proinflammatory cytokine serum level and COVID-19 symptoms within the Palestinian population. In cross-sectional study, serum samples of 27 non-hospitalized patients and 63 hospitalized patients SARS-CoV-2 infected patients, were tested for total antibodies, IL-6, TNF-α, IFN-γ and IL-1β using the ELISA test. Results showed that most common symptoms within patients were Joint pain, cough, and fever (73.3%, 69.7% and 50% respectively). Serum total antibodies (IGs) levels in non-hospitalized patients were higher than hospitalized patients ((44.7 COI and 9.2 COI). TNF-α and IL-6 were lower in non-hospitalized patients compared to hospitalized patients (48±17.9 pg/ml, 193.3±350.5 pg/ml respectively). On the other hand, IFN-γ, in non-hospitalized patients (1±2 IU/ml) was significantly higher than hospitalized patients (0.4±0.26 IU/ml). IL-1β was slightly lower in hospitalized patients (8.8±13.6 pg/ml) compared to non-hospitalized patients (12.5±24.5 pg/ml). Common mild symptoms of COVID-10 were negatively associated with proinflammatory cytokines serum level. In conclusion as it with other populations worldwide, IL-6 and TNF-α are playing a major role in the complications of SARS-CoV-2 infection. Monitoring the two cytokines is crucial for management and treatment of complicated consequence of COVID-19.
A missense KCNQ1 Mutation Impairs Insulin Secretion in Neonatal Diabetes
Authors: Zhou Zhimin , Gong Maolian , Pande Amit , Lisewski Ulrike , Röpke Torsten , Purfürst Bettina , liang Lei , Jia Shiqi , Frühler Sebastian , Margineanu Anca , Zeng Chun , Zhu Han , Kühnen Peter , Khodaverdi Semik , Krill Winfried , Chen Wei , Sander Maike , Raile Klemens , Izsvak Zsuzsanna 
Published: August 2021

AbstractKCNQ1/Kv7 is a voltage-gated K+ channel that regulates heart rhythm, glucose and salt homeostasis. Mutations of KCNQ1 are primarily associated with long-QT syndrome and type 2 diabetes; however, thus far KCNQ1 mutations have not been associated with monogenetic diabetes. Here, we identified a homozygous KCNQ1 missense mutation (R397W) in an individual with permanent neonatal diabetes (PND). To identify the mechanisms that link the mutation to the disease, we introduced the mutation into human embryonic stem cells (hESCs), and used them to derived pancreatic β-like cells (hESC-β cell). In early β-like cells, we observed atypical membrane electrical activity, increased levels of cytoplasmic Ca2+, and a hypersecretion of insulin. Upon extended culture, their insulin secretion decreased and the number of apoptotic cells increased, resulting in a reduction in the numbers of β-like cells. Late-stage β-like cells exhibited a decrease in the expression of metabolic genes, e.g. HNF4α, PDX1 and GLUT1, providing a possible mechanism for β-cell dysfunction. Our study identifies KCNQ1 as a novel candidate gene of monogenetic diabetes and shows that KCNQ1 regulates β-cell function and survival.
Interactions between a mechanosensitive channel and cell wall integrity signaling influence pollen germination inArabidopsis thaliana
Authors: Wang Yanbing , Coomey Joshua , Miller Kari , Jensen Gregory S. , Haswell Elizabeth S. 
Published: August 2021

ABSTRACTCells employ multiple systems to maintain cellular integrity, including mechanosensitive (MS) ion channels and the cell wall integrity (CWI) pathway. Here, we use pollen as a model system to ask how these different mechanisms are interconnected at the cellular level. MscS-Like (MSL)8 is an MS channel required to protectArabidopsis thalianapollen from osmotic challenges duringin vitrorehydration, germination and tube growth. New CRISPR/Cas9 and artificial microRNA-generatedmsl8alleles produced unexpected pollen phenotypes, including the ability to germinate a tube after bursting, dramatic defects in cell wall structure and disorganized callose deposition at the germination site. We document complex genetic interactions betweenMSL8and two previously established components of the CWI pathway,MARIS, andANXUR1/2. Overexpression ofMARISR240C-FPsuppressed the bursting, germination, and callose deposition phenotypes ofmsl8mutant pollen. Nullmsl8alleles suppressed the internalized callose structures observed inMARISR240C-FPlines. Similarly,MSL8-YFPoverexpression suppressed bursting in theanxur1/2mutant background, whileanxur1/2alleles reduced the strong rings of callose around ungerminated pollen grains inMSL8-YFPover-expressors. These data show that MS ion channels modulate callose deposition in pollen and provides evidence that cell wall and membrane surveillance systems coordinate in a complex manner to maintain cell integrity.
Evolution of host-microbe cell adherence by receptor domain shuffling
Authors: Baker EmilyClare P. , Sayegh Ryan , Kohler Kristin M. , Borman Wyatt , Goodfellow Claire K. , Brush Eden R. , Barber Matthew F. 
Published: August 2021

ABSTRACTStable adherence to epithelial surfaces is required for colonization by diverse host-associated microbes. Successful attachment of pathogenic microbes via surface adhesin molecules is also the first step in many devastating infections. Despite the primacy of epithelial adherence in establishing host-microbe associations, the evolutionary processes that shape this crucial interface remain enigmatic. Carcinoembryonic antigen associated cell adhesion molecules (CEACAMs) encompass a multifunctional family of vertebrate cell surface proteins which are recurrent targets of bacterial surface adhesins at epithelial surfaces. Here we show that multiple members of the primate CEACAM family exhibit evidence of repeated natural selection at protein surfaces targeted by bacteria, consistent with pathogen-driven evolution. Inter-species diversity of CEACAM proteins, between even closely-related great apes, determines molecular interactions with a range of bacterial adhesins. Phylogenetic analyses reveal that repeated gene conversion of CEACAM extracellular domains during primate divergence plays a key role in limiting bacterial adhesin tropism. Moreover, we demonstrate that gene conversion has continued to shape CEACAM diversity within human populations, with abundant CEACAM1 variants mediating evasion of adhesins fromNeisseria gonorrhoeae, the causative agent of gonorrhea. Together this work reveals a mechanism by which gene conversion shapes first contact between microbes and animal hosts.