bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-carbocisteine can cause cholestasis with vanishing bile duct syndrome in children: A case report
Authors: Takaki Yugo , Murahashi Makoto , Honda Kei , Hirai Katsuki 
Published: November 2022

Rationale:
Vanishing bile duct syndrome (VBDS) is the acquired progressive destruction and disappearance of intrahepatic interlobular bile ducts in the absence of underlying liver or biliary tract disease, causing chronic cholestasis. Infections, drugs, toxins, malignant diseases, and certain immunological processes are associated with the development of this syndrome. There have been no reports of children developing VBDS as a consequence of the administration of L-carbocisteine.

Patient concerns:
A 9-year-old Japanese girl presented with fever, jaundice, and skin rash. Laboratory investigations revealed elevated levels of serum transaminases, γ-glutamyltransferase, and bilirubin. Histopathological features were consistent with a diagnosis of VBDS. Drug-induced lymphocyte stimulation tests (DLST) were positive for L-carbocisteine.

Diagnosis:
VBDS caused by L-carbocisteine.

Interventions:
Ursodeoxycholic acid and discontinuation of L-carbocisteine.

Outcomes:
The patient responded to treatment based upon discontinuation of L-carbocisteine and administration of ursodeoxycholic acid. Her transaminase and bilirubin levels were normalized gradually.

Lessons:
Physicians should be aware of the fact that L-carbocisteine can cause cholestasis with VBDS in children.
Early Lyme neuroborreliosis manifesting as brachial plexopathy and meningitis in Northwestern Ontario, Canada: A case report
Authors: Gu Kaien , Boodman Carl , Orr Pamela , Wuerz Terence 
Published: November 2022

Rationale:
Lyme disease is a tick-borne disease caused by the spirochete B. burgdorferi, and patients often present with symptoms comparable to a viral-like illness. The diagnosis can be challenging given its wide range of manifestations and diagnostic testing can take days or longer. Here, we present a case of Lyme disease presenting as brachial plexopathy and meningitis.

Patient concerns:
A 76-years-old male presented to a tertiary-care hospital with left arm weakness and neck pain.

Diagnosis:
Our patient was diagnosed with Lyme neuroborreliosis and had positive serology, including enzyme immunoassay and Western blot.

Interventions:
Our patient received 17 days of ceftriaxone (2g IV daily) followed by oral doxycycline (100mg bid).

Outcomes:
Over the subsequent year, our patient had eventual complete recovery in muscle strength and sensation, with slower improvement to the cervical neck and left arm pain.

Lessons:
Incidence of Lyme disease is increasing in North America, and the disease has a wide range of symptoms. Lyme neuroborreliosis (LNB) is 1 presentation and can present with early or late manifestations; clinicians should maintain a high index of suspicion and begin empiric treatment in individuals with a clinical syndrome consistent with LNB. Early LNB manifestations have onset within 6 months of infection and include cranial and peripheral neuropathy, radiculitis, and aseptic meningitis; late LNB encompasses a chronic encephalomyelitis.
Comparison of programmed intermittent epidural bolus injection and continuous epidural injection in controlling nighttime pain and improving sleep quality after thoracotomy
Authors: Lee Su-Sung , Baek Ji-Hye , Park Soon-Ji , Kim Hye-Jin , Kim Hee-Young , Byeon Gyeong-Jo 
Published: November 2022

Background:
Postoperative pain after open thoracotomy is known to be very severe and affects sleep quality. This study aimed to investigate the effects of a programmed intermittent epidural bolus injection versus continuous epidural injection for controlling nighttime pain and improving sleep quality after thoracotomy.

Methods:
Seventy-six patients scheduled for open thoracotomy for lung cancer or other lung diseases were enrolled. The participants were divided into 2 groups. Group A was continuously injected with 0.2% levobupivacaine at 1.1 mL/h, and group B was injected intermittently with 3 mL 0.2% levobupivacaine at 3 hours intervals through a thoracic epidural catheter via a programmed infusion pump. Within 48 hours after surgery, the degree of pain control using visual analog scale and the patients’ sleep conditions on postoperative day (POD) 0 and 1 were evaluated, and other adverse events were investigated.

Results:
On POD 1 night, the visual analog scale in group B showed lower than group A (P = .009). Comparison of time to fall asleep showed no differences between 2 groups. Total sleep time was no difference on POD 0 but was longer in group B than that in group A on POD 1 (P = .042). Awakening from sleep on POD 0 was lower in group B than that in group A (P = .033), and satisfaction with sleep quality on POD 0 was superior in group B compared to group A (P = .005). Postoperative nausea and vomiting occurred more frequently in group B than in group A (P = .018).

Conclusion:
The programmed intermittent epidural bolus technique of patient-controlled epidural analgesia reduces postoperative nighttime pain and improves sleep quality in patients undergoing thoracotomy for lung cancer or other lung diseases.
Effectiveness of exercise in reducing cerebral stroke risk factors: A systematic review and meta-analysis
Authors: Men Jie , Wang Wenjuan , Zhao Jian , Wen Jie , Hao Qingqing , Li Shufeng , Zou Shuangling 
Published: November 2022

Objectives:
This study aimed to explore the relationship between exercise and cerebral stroke and provide evidence for the prevention of cerebral stroke.

Materials/Methods:
All clinical trials of exercise intervention for atherosclerosis were systematically reviewed. Five major databases were searched to retrieve relevant studies from their inception to May 2022. According to the magnitude of heterogeneity, the random and fixed-effect models were used to test reasonably.

Results:
According to the inclusion and exclusion criteria, 1341 articles were screened and 13 articles involving 825 patients were identified. The result showed that in the randomized controlled trials carotid intima-media thickness index was lower in the exercise group (−0.04 mm, 95% confidence interval: −0.07 to −0.01). All were statistically significant (P < .005) and subgroup analysis showed that the intervention period and paper quality are sources of heterogeneity.

Conclusions:
The results of this systematic review suggest that exercise is associated with a slow increase in carotid intima-media thickness, which may provide evidence that exercise helps reduce cerebral stroke.
Acute Pancreatitis in Childhood
Authors: Boonthai Ampaipan , Tanpowpong Pornthep , Puttanapitak Chawintee , Aeesoa Suraida , Losty Paul D. , Molagool Sani 
Published: November 2022

Objectives
This study aimed to describe etiology, management, and health outcomes of children developing acute pancreatitis at a tertiary Thailand pediatric surgery center.

Methods
Medical case records of all index cases during 2006–2016 were analyzed and reported.

Results
There were 42 male and 37 female patients, with a mean (standard deviation) age of 10.4 (4.5) years, included in the study. Medications were the commonest etiology for 39.3% of acute pancreatitis attacks, 11.4% for biliary tract disease cases, and 8% for postinterventional studies. In 30% of cases, no cause(s) was defined. Sixty-two patients (78.5%) had elevated serum lipase on hospital admission, whereas only 30.4% showed a raised amylase. Hospital stay was 15 days (interquartile range, 6–27 days). Two major complications in the series were pseudocysts (8.8%) and necrotizing pancreatitis (7.6%). Etiological factors and/or antibiotics were not directly linked to any specific complications. Seventeen children (22.8%) had 1 recurrent episode of acute pancreatitis documented. Mortality rate in index cases was 28%, with a higher percentage harboring a preexisting illness (34.4% vs 5.6%; P = 0.01) and in male than in female patients (41% vs 14%; P = 0.01).

Conclusions
Deaths from pediatric acute pancreatitis are more prevalent in male individuals and those with a preexisting illness. Targeted strategies aimed at “highest-risk” patients may potentially offset mortality.
Fluid Resuscitation With Lactated Ringer's Solution Versus Normal Saline in Acute Pancreatitis
Authors: Kow Chia Siang , Burud Ismail Abdul Sattar , Hasan Syed Shahzad 
Published: November 2022

Objectives
We aimed to perform a systematic review and meta-analysis of randomized controlled trials to summarize the overall association between the choice of fluid (lactated Ringer's [LR] or normal saline [NS]) and clinical outcomes in patients with acute pancreatitis.

Methods
A systematic literature search was performed in electronic databases to identify eligible randomized controlled trials. Meta-analyses with the random-effects and IVhet models were used to estimate the pooled odds ratio (OR) for outcomes of interest with the administration of LR relative to NS, at 95% confidence intervals (CIs).

Results
There was a significant reduction in the odds of intensive care unit admission and development of local complications, respectively, with the administration of LR among hospitalized patients with acute pancreatitis relative to administration of NS (pooled ORs, 0.33 [95% CI, 0.13–0.81] and 0.43 [95% CI, 0.21–0.89], respectively).

Conclusions
Our findings are able to assist clinicians in the navigation of the proper choice of fluid in patients with acute pancreatitis.
Factors Affecting the Circulating Levels of Oxyntomodulin in Health and After Acute Pancreatitis
Authors: Bharmal Sakina H. , Ko Juyeon , Kimita Wandia , Cho Jaelim , Petrov Maxim S. 
Published: November 2022

Objectives
To investigate the factors associated with the circulating levels of oxyntomodulin in healthy individuals and individuals after an episode of acute pancreatitis (AP).

Methods
Blood samples were collected from all participants after an overnight fast and analyzed for 28 biomarkers. Participants also underwent comprehensive body composition analysis on a 3-T magnetic resonance imaging scanner. Regression analyses were done to investigate the associations between oxyntomodulin and the studied factors.

Results
The study included 105 individuals who had a primary diagnosis of AP and 58 healthy individuals. Peptide YY (B coefficient, 0.094; 95% confidence interval [95% CI], 0.164–0.123), pancreatic polypeptide (0.048; 95% CI, 0.030–0.066), and leptin (0.394; 95% CI, 0.128–0.661) had significant associations with oxyntomodulin in healthy individuals. Peptide YY was the most prominent factor associated with oxyntomodulin, explaining 60% of its variance in health. Cholecystokinin (0.014; 95% CI, 0.010–0.018), amylin (−0.107; 95% CI, −0.192 to −0.021), and glycated hemoglobin (−0.761; 95% CI, −1.249 to −0.273) had significant associations with oxyntomodulin in individuals after AP. Cholecystokinin was the most prominent factor associated with oxyntomodulin, explaining 44% of its variance after AP.

Conclusions
Factors affecting the circulating levels of oxyntomodulin are different in health and after AP. These insights will enable the determination of populations that benefit from oxyntomodulin therapeutics in the future.
Pro-fibrogenic role of alarmin high mobility group box 1 in HIV–hepatitis B virus coinfection
Authors: Singh Kasha P. , Pallett Laura J. , Singh Harsimran , Chen Antony , Otano Itziar , Duriez Marion , Rombouts Krista , Pinzani Massimo , Crane Megan , Fusai Giuseppe , Avihingsanon Anchalee , Lewin Sharon R. , Maini Mala K. 
Published: November 2022

Objective:
Liver disease is accelerated in people with HIV (PWH) with hepatitis B virus (HBV) coinfection. We hypothesized that liver fibrosis in HIV–HBV is triggered by increased hepatocyte apoptosis, microbial translocation and/or HIV/HBV viral products.

Design:
Sera from PWH with HBV coinfection versus from those with HBV only or putative mediators were used to examine the pathogenesis of liver disease in HIV-HBV.

Methods:
We applied sera from PWH and HBV coinfection versus HBV alone, or putative mediators (including HMGB1), to primary human hepatic stellate cells (hHSC) and examined pro-fibrogenic changes at the single cell level using flow cytometry. High mobility group box 1 (HMGB1) levels in the applied sera were assessed according to donor fibrosis stage.

Results:
Quantitative flow cytometric assessment of pro-fibrogenic and inflammatory changes at the single cell level revealed an enhanced capacity for sera from PWH with HBV coinfection to activate hHSC. This effect was recapitulated by lipopolysaccharide, HIV-gp120, hepatocyte conditioned-media and the alarmin HMGB1. Induction of hepatocyte cell death increased their pro-fibrogenic potential, an effect blocked by HMGB1 antagonist glycyrrhizic acid. Consistent with a role for this alarmin, HMGB1 levels were elevated in sera from PWH and hepatitis B coinfection compared to HBV alone and higher in those with HIV–HBV with liver fibrosis compared to those without.

Conclusions:
Sera from PWH and HBV coinfection have an enhanced capacity to activate primary hHSC. We identified an increase in circulating HMGB1 which, in addition to HIV-gp120 and translocated microbial products, drove pro-fibrogenic changes in hHSC, as mechanisms contributing to accelerated liver disease in HIV–HBV.
Favorable Outcomes in Older Recipients Receiving Simultaneous Pancreas Kidney Transplantation
Authors: Budhiraja Pooja , Heilman Raymond L. , Reddy Kunam S. , Jadlowiec Caroline C. , Khamash Hassan A. , Ninan Jacob , Reddy Swetha , Me Hay Me , Misra Suman , Katariya Nitin , Chakkera Harini A. 
Published: November 2022

Background.
The objective of this study was to compare the long-term outcomes of older (50–65 y) type 1 diabetics with body mass index <35 kg/m2 and type 2 diabetics with body mass index <30 kg/m2 who received simultaneous pancreas kidney transplantation (SPKT) versus living donor kidney transplants (LDKTs). All subjects had insulin-dependent diabetes.

Methods.
This is a retrospective single-center study from July 2003 to March 2021 with a median follow-up of 7.5 y.

Results.
There were 104 recipients in the SPKT and 80 in the LDKT group. The mean age was 56 y in SPKT and 58 y in LDKT. There were 55% male recipients in the SPKT group versus 75% in LDKT. The duration of diabetes was 32 y in SPKT versus 25 y in LDKT. The number of preemptive transplants and length of dialysis were similar. However, the wait time was shorter for LDKT (269 versus 460 d). Forty-nine percent of the LDKT recipients received the organ within 6 mo of being waitlisted compared with 28% of SPKT recipients (P = 0.001). Donor age was lower in the SPKT group (27 versus 41 y). The estimated 5-y death censored kidney survival was 92% versus 98%, and 5-y patient survival was 86% versus 89% for SPKT versus LDKT. Death censored kidney and patient survival, acute kidney rejection by 1 y, and BK viremia were similar between the 2 groups. There were 17 pancreas graft losses within 1 y of transplant, the majority related to surgical complications, and it was not associated with increased mortality.

Conclusions.
SPKT in selected recipients aged 50 and above can have excellent outcomes similar to LDKT recipients.
Binding site plasticity regulation of the FimH catch-bond mechanism
Authors: Languin–Cattoën Olivier , Sterpone Fabio , Stirnemann Guillaume 
Published: November 2022

AbstractThe bacterial fimbrial adhesin FimH is a remarkable and well-studied catch-bond protein found at the tip ofE. colitype 1 pili, which allows pathogenic strains involved in urinary tract infections to bind high-mannose glycans exposed on human epithelia. The catch-bond behavior of FimH, where the strength of the interaction increases when a force is applied to separate the two partners, enables the bacteria to resist clearance when they are subjected to shear forces induced by urine flow. Two decades of experimental studies performed at the single-molecule level, as well as X-ray crystallography and modeling studies, have led to a consensus picture whereby force separates the binding domain from an inhibitor domain, effectively triggering an allosteric conformational change in the former. This force-induced allostery is thought to be responsible for an increased binding affinity at the core of the catch-bond mechanism. However, some important questions remain, the most challenging one being that the crystal structures corresponding to these two allosteric states show almost superimposable binding-site geometries, which questions the molecular origin for the large difference in affinity. Using molecular dynamics with a combination of enhanced-sampling techniques, we demonstrate that the static picture provided by the crystal structures conceals a variety of binding-site conformations that have a key impact on the apparent affinity. Crucially, the respective populations in each of these conformations are very different between the two allosteric states of the binding domain, which can then be related to experimental affinity measurements. We also evidence a previously unappreciated but important effect: in addition to the well-established role of the force as an allosteric regulator via domain separation, application of force tends to directly favor the high-affinity binding-site conformations. We hypothesize that this additionallocalcatch-bond effect could delay unbinding between the bacteria and the host cell before theglobalallosteric transition occurs, as well as stabilizing the complex even more once in the high-affinity allosteric state.
SpikeScape: A Tool for Analyzing Structural Diversity in Experimental Structures of the SARS-CoV-2 Spike Glycoprotein
Authors: Stepanenko Darya , Simmerling Carlos 
Published: November 2022

AbstractIn this application note we describe a tool which we developed to help structural biologists who study the SARS-CoV-2 spike glycoprotein. There are more than 500 structures of this protein available in the Protein Data Bank. These structures are available in different flavors: wild type spike, different variants, 2P substitutions, structures with bound antibodies, structures with Receptor Binding Domains in closed or open conformation, etc. Understanding differences between these structures could provide insight to how the spike structure changes in different variants or upon interaction with different molecules such as receptors or antibodies. However, inconsistencies among deposited structures, such as different chain or sequence numbering, hamper a straightforward comparison of all structures. The tool described in this note fixes those inconsistencies and calculates the distribution of the requested distance between any two atoms across all SARS-CoV-2 spike structures available in the Protein Data Bank, with the option to filter by various selections. The tool provides a histogram and cumulative frequency of the calculated distribution, as the ability to download the results and corresponding PDB IDs.
Mycobacteria form viable cell wall-deficient cells that are undetectable by conventional diagnostics
Authors: Dannenberg Noortje , Carrion Bravo Victor J. , Weijers Tom , Spaink Herman P. , Ottenhoff Tom H. M. , Briegel Ariane , Claessen Dennis 
Published: November 2022

ABSTRACTThe cell wall is a unifying trait in bacteria and provides protection against environmental insults. Therefore, the wall is considered essential for most bacteria. Despite this critical role, many bacteria can transiently shed their cell wall and recent observations suggest a link of such wall-deficient cells to chronic infections. Whether shedding the cell wall also occurs in mycobacteria has not been established unambiguously. Here we provide compelling evidence that a wide range of mycobacterial species, including clinical and non-clinical isolates, form viable cell wall-deficient cells in response to environmental stressors. Using cryo-transmission electron micrography we show that the complex multi-layered wall is largely lost in such cells. Notably, we show that their formation inMycobacterium marinumand BCG vaccine strains ofMycobacterium bovisis stimulated by exposure to cell wall-targeting antibiotics. Given that these wall-deficient mycobacteria are undetectable using conventional diagnostic methods, such cells have likely been overlooked in clinical settings. Altogether, these results indicate that mycobacteria can readily switch between a walled and wall-deficient lifestyle, which provides a plausible explanation for enabling persistence of infections caused by members of this genus.
Genome-wide analysis of the dynamic and biophysical properties of chromatin and nuclear proteins in living cells with Hi-D
Authors: Valades-Cruz Cesar Augusto , Barth Roman , Abdellah Marwan , Shaban Haitham A. 
Published: November 2022

AbstractTo understand the dynamic nature of the genome in real-time, the localization and rearrangement of DNA and DNA-binding proteins must be analyzed across the entire nucleus of single living cells. Recently, we developed a new computational light microscopy technique, called high-resolution diffusion mapping (Hi-D), that can accurately detect, classify, and map the types of diffusion and biophysical parameters such as the diffusion constant, anomalous exponent, drift velocity, and physical diffusion models at a high spatial resolution over the entire genome in living cells. Hi-D combines dense optical flow to detect and track local chromatin and protein motion, and Bayesian inference to characterize this local movement at nanoscale resolution. The initial implementation requires solid experience using MATLAB (MathWorks) and computational resources, for instance, access to a computer cluster, to perform the Hi-D analysis. In addition, this implementation takes ∼18-24 hours to analyze a typical imaging stack. To avoid these limitations and emphasize high-performance implementation, we present a customized version called Hi-D-Py. The new implementation is written in the open-source Python programming language and has an option for parallelizing the calculations to run on multi-core CPUs. The functionality of Hi-D-Py is exposed to the users via user-friendly documented Python notebooks. Our efficient implementation reduces the analysis time to less than one hour using a multi-core CPU with a single compute node. We also present different applications of Hi-D for live-imaging of DNA, H2B, and RNA Pol II sequences acquired with spinning disk confocal and super-resolution structured illumination microscopy.