bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibroscan® and Shear Wave correlated well in hepatic fibrosis evaluation of patients with chronic liver diseases “in real life situation”
Authors: Zougmoré Honoré Tegwendé , Cadranel Jean François David , Fantognon Gildas , Azzi Badia , Smadhi Ryad , Ngele Efole Jean René , Mrabti Samir , Heng Ratmony , Ntsama Marie Adrienne , Medmoun Mourad , Kazerouni Firouzeh , Le Magoarou Tristan
Published: August 2022

Background:

A new noninvasive medical device based on ultrasound elastography such as the Shear Wave Elastography (SWE) was designed in order to measure the liver hardness. The purpose of this work was to evaluate the correlation of the results of the liver elasticity measurements obtained by Fibroscan® (FS) and SWE for patients with chronic liver diseases.

Methods:

Between January and October 2017, the patients who were followed during this period of time underwent noninvasive assessments of liver fibrosis by SWE in the intercostal spaces during abdominal ultrasound procedures and/or FS. The correlation between FS and SWE was estimated and tested at a 0.05 significance level.

Results:

Four hundred and seventy-six patients were included in this study. The main etiologies of chronic liver disease were non alcoholic fatty disease (NAFLD), chronic viral hepatitis B (HBV) and chronic viral hepatitis C (HCV). All patients underwent a SWE and 167 among them underwent a FS procedure. The patients who were followed revealed a median FS measurement of 5.80 kpa (Q25 = 4.90 kPa; Q75 = 8 kPa) and a median SWE measurement of 7.00 kPa (Q25 = 6.10 kPa; Q75 = 8.10 kPa). We could observe a significant correlation between the FS and SWE measurements (0.49; P = .001) in the total cohort. The average absolute difference between the measurements of these 2 methods was of 2.54 kPa (sd = 3.39). There was no significant correlation for patients with NAFLD no matter whether they presented with signs of suspected non alcoholic steatohepatitis (NASH) or not (R = 0.20; P = .108). All patients intending to perform the examination were able to undergo the SWE, allowing 33.3% of the patients who failed the FS to have a noninvasive evaluation of their fibrosis.

Conclusion:

The SWE technique proved to be as efficient as the FS one for the evaluation of the liver fibrosis in real life situation.
Increased NOX1 and DUOX2 expression in the colonic mucosa of patients with chronic functional constipation
Authors: Wei Xiuqin , Xue Mei , Kang Chunbo , Gao Lei , Zhang Mengqiao , Ma Chao , Jia Wei , Zheng Yufeng , Cao Lei , Chen Pan , Jiang Shujing , Chu Fong-Fong , Gao Qiang
Published: August 2022

To determine whether oxidative stress and inflammation are associated with constipation by examining the expression of the main producers of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, and pro-inflammatory cytokines in the colon of patients with chronic functional constipation.

The colonic biopsies were collected from 32 patients with chronic functional constipation and 30 healthy subjects who underwent colonoscopy. Colonic mucosal histology was observed. Interleukin (IL)-1β, IL-6, IL-8 messenger RNA (mRNA), and 4 members of NADPH oxidase (NOX1, NOX2, DUOX2, and NOX4) protein and mRNA were assessed by immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction.

The tissues from both patients and healthy subjects showed normal histological structure without increase of inflammatory cells. NOX1 protein and mRNA levels were significantly increased compared to controls (P < .05). DUOX2 protein, but not mRNA, was increased by 2-fold compared to controls (P < .05). The levels of NOX2 and NOX4 protein and mRNA demonstrated no significant difference between patients and control subjects. The levels of IL-1β and IL-6 mRNA were significantly higher in constipation patients (P < .05), while IL-8 mRNA level was no different between the 2 groups.

NADPH oxidase and pro-inflammatory cytokine might be involved in the pathogeneses of chronic functional constipation.
Transformation from polycythemia vera to acute promyelocytic leukemia: Case report and literature review
Authors: Li Wen-Wen , Sui Xiu-Fang , Fan Shuang , Xu Hong , Wang Cheng-Lei , Wang Fei-Ying , Mo Xiao-Dong
Published: August 2022

Introduction:

Transformation from chronic myeloproliferative neoplasm to acute leukemia is a feature of myeloproliferative neoplasm; however, the rate is not high. Transformation to acute promyelocytic leukemia is rare. Here, we report a case of transformation of polycythemia vera to acute promyelocytic leukemia and describe a process of clonal evolution that has not yet been reported.

Patient concerns:

In this case, a 51-year-old woman was diagnosed with polycythemia vera and concomitant JAK2/V617F mutations in July 2019. She underwent intermittent phlebotomy and oral hydroxyurea irregularly. After 2 years, the patient complained of fatigue and poor sleep quality for 2 months.

Diagnosis:

Further examination revealed marked hypercellularity and grade 1 bone marrow fibrosis with the PML/RARαV variant (23.85% mutation load), WT1-Exon1 (37.8%), WT1-Exon9 (4.1%), JAK3-Exon7 (49.3%), and RELN-Exon55 (45.8%). According to the World Health Organization classification of tumors of hematopoietic and lymphoid tissues, the patient was ultimately diagnosed with a rare transformation of polycythemia vera to acute promyelocytic leukemia.

Interventions:

The patient underwent dual induction therapy with all-trans-retinoic acid and arsenic trioxide.

Outcomes:

After 28 days of induction therapy, the patient achieved complete remission, was compliant and the treatment was well tolerated.

Conclusion:

Polycythemia vera can transform into acute promyelocytic leukemia; therefore, it is important to review bone aspiration and other tests to perform a comprehensive assessment and monitor the disease status, to detect disease progression and intervene early when it transforms into acute promyelocytic leukemia.
Medicaid Expansion and Change in Federally Qualified Health Center Accessibility from 2008 to 2016
Authors: Evans Leigh , Fabian M. Patricia , Charns Martin P. , Gurewich Deborah , Stopka Thomas J. , Cabral Howard J.
Published: August 2022

Background:

The Affordable Care Act expanded health coverage for low-income residents through Medicaid expansion and increased funding for Health Center Program New Access Points from 2009 to 2015, improving federally qualified health center (FQHC) accessibility. The extent to which these provisions progressed synergistically as intended when states could opt out of Medicaid expansion is unknown.

Objective:

To compare change in FQHC accessibility among census tracts in Medicaid expansion and nonexpansion states.

Research Design:

Tract-level FQHC accessibility scores for 2008 and 2016 were estimated applying the 2-step floating catchment area method to American Community Survey and Health Resources and Services Administration data. Multivariable linear regression compared changes in FQHC accessibility between tracts in Medicaid expansion and nonexpansion states, adjusting for sociodemographic and health system factors and accounting for state-level clustering.

Subjects:

In total, 7058 census tracts across 10 states.

Results:

FQHC accessibility increased comparably among tracts in Medicaid expansion and nonexpansion states (coef: 0.3; 95% CI: −0.3, 0.8; P-value: 0.36). FQHC accessibility increased more in tracts with higher poverty and uninsured rates, and those with lower proportions of non-English speakers and Black or African American residents.

Conclusion:

Similar gains in FQHC accessibility across Medicaid expansion and nonexpansion states indicate improvements progressed independently from Medicaid expansion, rather than synergistically as expected. Accessibility increases appeared consistent with HRSA’s goal to improve access for individuals experiencing economic barriers to health care but not for those experiencing cultural or language barriers to health care.
Health Care Professionals' Perceptions of Caring for Patients with Substance Use Disorders during Pregnancy
Authors: Merritt Elizabeth L. , Burduli Ekaterina , Purath Janet , Smart Denise
Published: August 2022

Purpose:

Pregnant patients with substance use disorders (SUDs) may experience stigma and implicit and explicit bias from health care professionals when seeking prenatal care. This study explored the perceptions of health care professionals caring for pregnant women with SUDs and examined changes in their perceptions over time following attendance at an educational conference about SUDs.

Study Design and Methods:

Evidence-based education was presented to health care professionals at a conference to reinforce the complex needs of pregnant women with SUDs. An adapted version of the Attitudes of Healthcare Providers Survey (AHPS) was administered at three intervals and assessed health care professionals' perceptions of pregnant women with SUDs. Data from the three time points were analyzed using repeated measures ANOVA.

Results:

There was a significant decrease in mean AHPS scores between T1 (38.24 ± 8.93) and T2 (32.71 ± 7.77), p < .05, and then a significant increase in mean AHPS score between T2 and T3 (37.08 ± 8.45), p < .05. High mean scores on health care professionals' knowledge and competence were noted after the educational intervention but were not sustained over time.

Clinical Implications:

Education cannot change health care professional perceptions of pregnant individuals with SUD. Health care professionals need access to additional clinical and community resources. Nurse leaders must continue to advocate for institutional and community resources to meet referral, treatment, and follow-up needs during pregnancy. Reducing perceptions of stigma and acknowledging the impact of implicit bias toward pregnant women with SUD may reduce barriers and improve their care.
Correlation of H3K9ac and H4K12ac With Cell Proliferation Marker Ki-67 in Oral Leukoplakia: An Immunohistochemical Study
Authors: Espinosa Roberta C.G. , Costa Anaíra R.G.F. , Garcia Júnior Marcelo A. , Ribeiro Rosy I.M. de A. , Cardoso Sérgio V. , de Faria Paulo R. , Loyola Adriano M.
Published: August 2022

This study aimed to analyze the immunohistochemical expression of H3K9ac and H4K12ac in oral leukoplakia (OL) and its association with cell proliferation marker Ki-67 and clinicopathologic data. Paraffin-embedded, formalin-fixed tissue samples from 50 OLs and 15 fragments of the normal oral mucosa (NOM) were submitted to immunohistochemical assay using the streptavidin-biotin-peroxidase method. Quantitative analysis of the antigen-antibody reaction was performed by obtaining integrated optical density (IOD) and the percentage of positive nuclei (PPN) with ImageJ software. OL samples presented higher PPN (P=0.02) and lower IOD values (P=0.007) for H4K12ac in comparison to NOM. The area under the receiver operating characteristic curve for PPN and IOD values of H4K12ac immunostaining were 0.70 (P=0.02) and 0.73 (P=0.007), respectively. No differences were found between OL and NOM for H3K9ac. Cell proliferation marker Ki-67 had a positive correlation with PPN (P<0.0001) and IOD (P=0.0007) for H3K9ac expression and with IOD values (P=0.002) for H4K12ac expression. The present findings suggest that alterations in the acetylation pattern of H4K12 occur in the early stages of oral carcinogenesis and that both H3K9ac and H4K12ac might have a role in the regulation of epithelial cell proliferation of OL.
Controlled attenuation parameter accurately detects liver steatosis in people with HIV
Authors: Duarte Maria , Tien Phyllis , Ma Yifei , Noworolski Susan M. , Korn Natalie , Price Jennifer C.
Published: August 2022

Objectives:

Hepatic steatosis is a leading cause of cirrhosis and hepatocellular carcinoma and is highly prevalent in persons with HIV (PWH). However, most studies of hepatic steatosis diagnosis in PWH have focused on those at high risk. We determined the accuracy of vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP) in detecting mild or greater hepatic steatosis as compared with the noninvasive gold standard magnetic resonance spectroscopy (MRS) in PWH.

Methods:

Among 149 participants with and without HIV, we evaluated test characteristics of CAP and calculated serum indices Hepatic Steatosis Index (HSI) and STEATO-ELSA in identifying 3T MRS-measured hepatic steatosis (defined as a liver fat fraction ≥5%).

Results:

Most participants were women and over half were African American. Median BMI was 27 kg/m2. Hepatic steatosis prevalence by MRS and CAP (cutoff 248 dB/m) was 36% and 47%, respectively. CAP had an AUROC of 0.82, and the at least 248 dB/m cutoff yielded a sensitivity, specificity, positive-predictive value, and negative-predictive value of 83%, 72%, 61%, and 88%, respectively. These test characteristics were not statistically different from the optimal cutoff of at least 252 dB/m. Higher waist circumference, greater visceral adipose tissue, heavy alcohol use, and VCTE scans flagged as having the probe positioned too low were associated with CAP and MRS discordance. Serum indices of hepatic steatosis had slightly worse performance characteristics than CAP.

Conclusion:

CAP may be an effective alternative to MRS for noninvasive hepatic steatosis assessment in PWH. The commonly used CAP cutoff of at least 248 dB/m to diagnose hepatic steatosis can be used in PWH.
Three-dimensional Assessment of Autologous Calvarial Bone Grafting for Alveolar Clefts Reconstruction in Pediatric Population: A Retrospective Study
Authors: Bagnarosa Tony , Ferri Joël , Grégoire Gaspard , Baralle Marie-Madeleine , Drumez Elodie , Touzet-Roumazeille Sandrine
Published: August 2022

Reconstruction of alveolar clefts using cancellous bone graft is associated with a high rate of resorption. The aim of this study was to evaluate the osseointegration capacity of cortical calvarial bone grafting using 3-dimensional imaging assessment for alveolar cleft reconstruction in pediatric population.All alveolar bone grafting procedures performed between January 2015 and October 2017 in the maxillofacial surgery department of Lille University Hospital were included. All patients were evaluated clinically and by 3-dimensional imaging before bone grafting and at 3 months after surgery. Cleft and bone graft volumes were assessed using Horos software, v. 3.3.5, through a segmentation process. The bone filled ratio at 3 months after surgery was calculated. A total of 48 alveolar bone grafting procedures were performed in 37 patients: 3 unilateral cleft lip and alveolar, 20 unilateral cleft lip and palate, and 25 bilateral full cleft lip and palate (3 patients had only unilateral surgery). The mean bone filled ratio was 72.27%±23.65%, 81% for unilateral cleft lip and alveolus, 75.4%±20.6 for unilateral cleft lip and palate, and 65.5%±30 for bilateral complete cleft lip and palate (P =0.1981). Calvarial bone grafting seems to be a relevant alternative to other donor sites for alveolar cleft reconstruction.
Biliary Tract Exploration After Laparoscopic Left-sided Hepatectomy: A Comparative Study of Left Hepatic Duct Orifice Versus Common Bile Duct Approach
Authors: Tu Shuju , Sun Gen , Fang Kang , Xin Wanpeng , Zha Ming , Wan Renhua , Li Yong , Xiao Weidong
Published: August 2022

Background:

Laparoscopic left-sided hepatectomy (LLH) and additional biliary tract exploration are effective methods to treat left-sided hepatolithiasis (LSH) combined with extrahepatic bile duct stones. Although biliary tract exploration through common bile duct (CBD) incision has been widely accepted, the safety and effectiveness of the left hepatic duct (LHD) orifice approach after LLH is still in debate.

Methods:

One hundred and forty-four patients with LSH who underwent LLH and biliary tract exploration in our institution from April 2014 to September 2021 were enrolled in the retrospectively study. They were divided into 3 groups: LHD group (n=67), CBD/T-tube group (n=58), and CBD/PC group (n=19). Patients’ demographic characteristics, intraoperative, and postoperative outcomes were retrospectively analyzed.

Results:

LHD group exhibited a shorter operative time (202.8±42.2 vs. 232.7±47.5 min, P=0.000), time to first bowel movement (2.3±0.5 vs. 2.9±0.7 d, P=0.000) and postoperative hospital stay (7.5±2.1 vs. 9.8±5.2 d, P=0.001) compared with the CBD/T-tube group. The lithotomy time in the LHD group was significantly longer than that in the CBD/T-tube group (33.6±7.3 vs. 29.0±6.3 min, P=0.000) and CBD/PC group (33.6±7.3 vs. 28.7±3.7, P=0.006). Intraoperative blood loss, blood transfusion rate, initial stone clearance rate, and stone recurrence rate all had no significant differences between the 3 groups (all P>0.05). LHD group showed less rate of electrolyte imbalance than that of the CBD/T-tube group (3.0% vs. 19.0%, P=0.004) but it was equivalent to the CBD/PC group (P>0.05). The type of biliary tract exploration (odds ratio: 5.43, 95% confidence interval: 0.04-0.95, P=0.032) as independent predictors of electrolyte imbalance. No reoperation and mortality occurred in the 3 groups. The conversion rate was comparable among 3 groups (1.5% vs. 1.7% vs. 0, all P>0.05). No significant difference in stone recurrence rate was seen (1.5% vs. 3.4% vs. 0, all P>0.05).

Conclusion:

Biliary tract exploration through LHD orifice after LLH is a safe and effective treatment for selected patients with LSH, with an advantage over the T-tube drainage in the field of operative time, the incidence of electrolyte imbalance, recovery of gastrointestinal function, and postoperative hospital stay.
A Practically Modified Approach with Complete Posterior Mobilization for Three-port Sleeve Gastrectomy: Single-center Experience
Authors: Pan Hsin-Mei , Liao Guo-Shiou , Lin Chien-Hua , Feng Ting-Yuan , Hsu Fang-Chin , Chang Po-Chih , Hsu Kuo-Feng
Published: August 2022

Background:

Although the procedure of laparoscopic sleeve gastrectomy (LSG) has been standardized either in conventional lateral to medial or medial to lateral approach, surgeons occasionally face the challenge of poor visualization of the His angle and difficulty in complete posterior mobilization in limited surgical field. This study aimed to introduce our novel details of modified approach to address these issues.

Methods:

One hundred patients with obesity underwent modified approach- three-port laparoscopic sleeve gastrectomy. Herein, we demonstrated our method to ease the procedure of gastric fundus mobilization with extensive posterior mobilization (shown in video, Supplemental Digital Content 1, http://links.lww.com/SLE/A336). The demographic characteristics and perioperative data were reviewed.

Results:

There was no case of conversion to open surgery. The mean operative time, volume of blood loss, and hospital stay were 72.5±22.7 minutes, 11.6±10.5 mL, and 4.3±2.1 days, respectively. One postoperative leakage was observed and it was successfully treated with metallic covered stent. The percentage of total weight loss at 6 months and 1 year were 20.3±8.4 and 29.8±9.2, respectively.

Conclusions:

Our experience showed that the modified technique is feasible and may help surgeons to accomplish a complete posterior mobilization, and better address the poor visualization of the the His angle-site owing to the interposition of floating omentum or bulging part of the stomach.
Registry of the International Society of Uterus Transplantation: First Report
Authors: Brännström Mats , Tullius Stefan G. , Brucker Sara , Dahm-Kähler Pernilla , Flyckt Rebecca , Kisu Iori , Andraus Wellington , Wei Li , Carmona Francisco , Ayoubi Jean-Marc , Scollo Paolo , Weyers Steven , Fronek Jiri
Published: August 2022

Background.

Uterus transplantation (UTx) is a novel type of transplantation to treat infertility in women with an absent or nonfunctioning uterus. The International Society of Uterus Transplantation (ISUTx) has developed a registry to monitor worldwide UTx activities while serving as a repository for specific research questions.

Methods.

The web-based registry has separate data fields for donor, recipient, surgeries, immunosuppression, rejections, pregnancies with live birth(s), and transplant hysterectomies. Data are prospectively registered.

Results.

A total of 45 UTx procedures have been registered; the majority (78%) of those procedures were live donor (LD) transplants. Median age of the LDs, deceased donors, and recipients were 50 y (range 32–62), 38.5 y (19–57), and 29 y (22–38), respectively. The duration of LD surgery was approximately twice as long as the recipient surgery. Postoperative complications of any Clavien-Dindo grade were registered in 20% of LDs and 24% of recipients. Rejection episodes were more frequent (33%) early after transplantation (months 1–5) compared with later time points (months 6–10; 21%). Healthy neonates were delivered by 16 recipients, with 3 women giving birth twice. The total live birth rate per embryo transfer was 35.8%. Median length of pregnancy was 35 gestational weeks. Twelve uteri were removed without childbirth, with 9 transplant hysterectomies occurring during the initial 7 mo post-UTx.

Conclusions.

A mandatory registry is critical to determine quality and process improvement for any novel transplantation. This registry provides a detailed analysis of 45 UTx procedures performed worldwide with a thorough analysis of outcomes and complications.
Nasogastric tube care and flushing in a Portuguese general medicine ward: a best practice implementation project
Authors: Fernandes António M. , Henriques Pedro , Lourenço Ana R. , Mateus Fernando , Santos Joana , Marques Daniela , Apóstolo João L.A. , Cardoso Daniela F.B. , Klugar Miloslav , Klugarová Jitka
Published: August 2022

Objectives:

To implement evidence-based practice related to care and flushing of nasogastric tubes inserted for feeding, in a general medicine ward.

Introduction:

Nasogastric tube feeding is a widely used nutritional support form. Although performed by qualified professionals, it is not a harm-free intervention. Progression to the trachea during initial insertion, aspiration of gastric contents, improper position for patient feeding, and/or a blocked tube are examples of problems that can occur.

Methods:

The project used JBI's methodological approach of the Clinical Evidence System and Getting Research into Practice audit and feedback tool. A baseline audit focused on nursing procedures related to the maintenance of nasogastric tube feeding, based on 14 criteria informed by the JBI evidence summaries, was performed for a month. Education sessions and other engagement strategies and resources were used to increase nasogastric tube maintenance. This best-practice implementation was conducted in Portugal, between January 2020 and April 2021, in a 33-bed general medicine ward with a staff of 30 registered nurses.

Results:

Different samples, for each audited procedure, were obtained from a universe of 25 nurses and 14 episodes of patients with nasogastric tube in baseline and 10 in follow-up audit. At baseline, compliance with the criteria ranged from 0 to 88%. Ten of the 14 criteria were below 50%. The follow-up audit showed significant improvement in all compliance criteria (ranging from 44.4 to 100%). Criteria 1 and 2, which were aimed at preventing adverse consequences related to wrong placement or displacement of the nasogastric tube, showed a high postimplementation compliance level (89.3 and 90%).

Conclusion:

With an integrated plan incorporating interventions, strategies, and resources, tailored for this context, we improved nurses’ knowledge of nasogastric tube maintenance and achieved significantly increased compliance with nasogastric tube care best-practice. We suggest maintaining current strategies, and reinforcing clinical supervision and regular assessment.
Optimization of Klebsiella pneumoniae Biofilm Preservation for Scanning Electron Microscopy Reveals Impact of Capsule on Biofilm Formation.
Authors: Fleeman Renee M , Mikesh Michelle , Davies Bryan W
Published: August 2022

Klebsiella pneumoniae biofilm formation is associated with chronic and relapsing infections. Scanning electron microscopy (SEM) is a powerful tool for characterizing biofilm structure and studying their formation. Reliable visualization of biofilm structure requires careful sample preservation, otherwise there may be loss of non-covalent interactions that are susceptible to damage during the dehydration and washing preparation steps. However, no standard procedure has been adopted in literature to fix K. pneumoniae biofilm for scanning electron microscopy studies. This lack of standardization makes it challenging to compare results between studies and determine if optimal fixation methods have been achieved to preserve native structures. To advance this critical area of study, we describe a scanning electron microscopy fixation method optimized for K. pneumoniae biofilm preservation. Our study reveals the importance of optimizing the biofilm preparation steps before scanning electron microscopy to observe differences in biofilm architecture between strains. Using our optimized fixation, we show that although species that overproduce capsular extracellular polysaccharides produced more robust biofilms, K. pneumoniae can form a developed biofilm in the absence of capsular polysaccharides.
Does phasic dopamine release cause policy updates?
Authors: Carter Francis , Cossette Marie-Pierre , Trujillo-Pisanty Ivan , Pallikaras Vasilios , Breton Yannick-André , Conover Kent , Caplan Jill , Solis Pavel , Voisard Jacques , Yaksich Alexandra , Shizgal Peter
Published: August 2022

Phasic dopamine activity is believed to both encode reward-prediction errors (RPEs) and to cause the adaptations that these errors engender. If so, a rat working for optogenetic stimulation of dopamine neurons will repeatedly update its policy and/or action values, thus iteratively increasing its work rate. Here, we challenge this view by demonstrating stable, non-maximal work rates in the face of repeated optogenetic stimulation of midbrain dopamine neurons. Furthermore, we show that rats learn to discriminate between world states distinguished only by their history of dopamine activation. Comparison of these results to reinforcement learning simulations suggests that the induced dopamine transients acted more as rewards than RPEs. However, pursuit of dopaminergic stimulation drifted upwards over a time scale of days and weeks, despite its stability within trials. To reconcile the results with prior findings, we consider multiple roles for dopamine signaling.
Early activation of cellular stress and death pathways caused by cytoplasmic TDP-43 in the rNLS8 mouse model of ALS/FTD
Authors: Luan Wei , Wright Amanda L. , Brown-Wright Heledd , Le Sheng , Gil Rebecca San , Martin Lidia Madrid San , Ling Karen , Jafar-Nejad Paymaan , Rigo Frank , Walker Adam K.
Published: August 2022

TAR DNA binding protein 43 (TDP-43) pathology is a key feature of over 95% of amyotrophic lateral sclerosis (ALS) and nearly half of frontotemporal dementia (FTD) cases. The pathogenic mechanisms of TDP-43 dysfunction are poorly understood, however activation of cell stress pathways may contribute to pathogenesis. We therefore sought to identify which cell stress components are critical for driving disease onset and neurodegeneration in ALS/FTD. We studied the rNLS8 transgenic mouse model, which expresses human TDP-43 with a genetically-ablated nuclear localisation sequence within neurons of the brain and spinal cord resulting in cytoplasmic TDP-43 pathology and progressive motor dysfunction. Amongst numerous cell stress-related biological pathways profiled using qPCR arrays, several critical ISR effectors, including CCAAT/enhancer-binding homologous protein (Chop/Ddit3) and activating transcription factor 4 (Atf4), were upregulated in the cortex of rNLS8 mice prior to disease onset. This was accompanied by early up-regulation of anti-apoptotic gene Bcl2 and diverse pro-apoptotic genes including BH3-interacting domain death agonist (Bid). However, pro-apoptotic signalling predominated after onset of motor phenotypes. Notably, pro-apoptotic caspase-3 protein was elevated in the cortex of rNLS8 mice at later disease stages, suggesting that downstream activation of apoptosis drives neurodegeneration following failure of early protective responses. Unexpectedly, suppression of Chop in the brain and spinal cord using antisense oligonucleotide-mediated silencing had no effect on overall TDP-43 pathology or disease phenotypes in rNLS8 mice. Cytoplasmic TDP-43 accumulation therefore causes very early activation of ISR and both anti-and pro-apoptotic signalling that switches to predominant pro-apoptotic activation later in disease. These findings suggest that precise temporal modulation of cell stress and death pathways may be beneficial to protect against neurodegeneration in ALS and FTD.

Key points

ISR genes Atf4 and Chop, anti-apoptotic Bcl2 and pro-apoptotic gene Bid, Bim, Noxa were upregulated in the cortex of rNLS8 mice prior to disease onset

Knockdown of Chop had limited effects on TDP-43 pathology and did not alter motor deficits in rNLS8 mice

Both anti-and pro-apoptotic genes are upregulated prior to disease onset, and switches to activation of pro-apoptotic signalling at later disease stages

Caspase-3 activation likely drives neurodegeneration in the cortex of rNLS8 mice
Right anterior insula effective connectivity impairs intrinsic BOLD fluctuations in dorsal attention network in adolescents and young adults with borderline personality symptoms
Authors: Hall Nathan T. , Hallquist Michael N.
Published: August 2022

Background

Borderline Personality Disorder (BPD) symptoms often emerge in adolescence. However, little is known about the functional organization of intrinsic brain networks in young people with BPD symptoms.

Methods

In this study we collected resting-state fMRI data in a sample of adolescents and young adults with (nBPD = 40) and without BPD (nHC= 42) symptoms. Using a detailed cortico-limbic parcellation coupled with graph theoretical analyses, we tested for group and age-related differences in regional functional and effective connectivity (FC, EC) and amplitude of low frequency fluctuations (ALFF). We conducted a series of analyses that progressed from global network properties to focal tests of EC amongst nodes in Salience (SN) and Dorsal Attention Networks (DAN).

Results

At the regional level, regularized regression analyses revealed a broad pattern of hyper-connectivity and heightened ALFF in R dorsal anterior insula (daIns), in addition to hypoconnectivity in R temporal-parietal junction (TPJ) and decreased ALFF in multiple DAN regions. Furthermore, analyses of EC amongst daIns, TPJ, and DAN revealed that in BPD participants daIns exerts a heightened influence on TPJ and DAN regions. Finally, multivariate mediation models indicated that lower DANALFF was differentially predicted by EC from TPJ and daIns.

Conclusions

Our findings provide converging evidence that heightened EC from daIns impairs network-wide ALFF in DAN both directly and indirectly via impaired TPJ functioning. We interpret this pattern of findings in line with an “attentional hijacking” account of borderline personality.
Dynamics of Pulsatile Activities of Arcuate Kisspeptin Neurons in Aging Female Mice
Authors: Goto Teppei , Hagihara Mitsue , Miyamichi Kazunari
Published: August 2022

Reproductive senescence is broadly observed across mammalian females, including humans, eventually leading to a loss of fertility. The pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is essential for gonad function, is primarily controlled by kisspeptin neurons in the hypothalamic arcuate nucleus (ARCkiss), the pulse generator of GnRH. The pulsatility of GnRH release, as assessed by the amount of circulating gonadotropin, is markedly reduced in aged animals, suggesting that the malfunctions of ARCkissmay be responsible for reproductive aging and menopause-related disorders. However, the activity dynamics of ARCkissduring the natural transition to reproductive senescence remain unclear. Herein, we introduce chronicin vivoCa2+imaging of ARCkissin female mice by fiber photometry to monitor the synchronous episodes of ARCkiss(SEskiss), a known hallmark of GnRH pulse generator activity, from the fully reproductive to acyclic phase over 1 year. During the reproductive phase, we find that not only the frequency, but also the intensities and waveforms of individual SEskiss, vary depending on the stage of the estrus cycle. During the transition to reproductive senescence, the integrity of SEskisspatterns, including the frequency and waveforms, remains mostly unchanged, whereas the intensities tend to decline. These data illuminate the temporal dynamics of ARCkissactivities in aging female mice. More generally, our findings demonstrate the utility of fiber-photometry-based chronic imaging of neuroendocrine regulators in the brain to characterize aging-associated malfunction.

Significance Statement

The transition to reproductive senescence significantly impacts the quality of life of women, but the underlying neural mechanisms remain poorly characterized. Goto and Miyamichi establish long-term (from the reproductive to acyclic phase) chronic imaging of the central pacemaker activities of reproductive functions by fiber photometry in female mice. In particular, they focus on kisspeptin neurons in the arcuate nucleus of the hypothalamus. Their data reveal that during the transition to reproductive senescence, the pulsatile activities of kisspeptin neurons show unexpected robustness in terms of frequency, but a tendency for the intensity to decline. Their findings exhibit the power of direct chronic visualization of hormonal regulators in the brain, which is generally applicable to facilitate studies of aging-associated malfunctions in neuroendocrine systems.
Ori-Finder 2022: A Comprehensive Web Server for Prediction and Analysis of Bacterial Replication Origins
Authors: Dong Meijing , Luo Hao , Gao Feng
Published: August 2022

The replication of DNA is a complex biological process that is essential for life. Bacterial DNA replication is initiated at genomic loci referred to as replication origins (oriCs). Integrating the Z-curve method, DnaA box distribution, and comparative genomic analysis, we developed a web server to predict bacterial oriCs in 2008 called Ori-Finder, which contributes to clarify the characteristics of bacterial oriCs. The oriCs of hundreds of sequenced bacterial genomes have been annotated in their genome reports using Ori-Finder and the predicted results have been deposited in DoriC, a manually curated database of oriCs. This has facilitated large-scale data mining of functional elements in oriCs and strand-biased analysis. Here, we describe Ori-Finder 2022 with updated prediction framework, interactive visualization module, new analysis module, and user-friendly interface. More species-specific indicator genes and functional elements of oriCs are integrated into the updated framework, which has also been redesigned to predict oriCs in draft genomes. The interactive visualization module displays more genomic information related to oriCs and their functional elements. The analysis module includes regulatory protein annotation, repeat sequence discovery, homologous oriC search, and strand-biased analyses. The redesigned interface provides additional customization options for oriC prediction. Ori-Finder 2022 is freely available at http://tubic.tju.edu.cn/Ori-Finder2022 and https://tubic.org/Ori-Finder2022.
Human DUX4 and mouse Dux interact with STAT1 and broadly inhibit interferon-stimulated gene induction
Authors: Spens Amy E. , Sutliff Nicholas A. , Bennett Sean R. , Campbell Amy E. , Tapscott Stephen J.
Published: August 2022

DUX4 activates the first wave of zygotic gene expression in the early embryo. Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral dystrophy (FSHD), whereas expression in cancers suppresses IFNγ-induction of MHC Class I and contributes to immune evasion. We show that the DUX4 protein interacts with STAT1 and broadly suppresses expression of IFNγ stimulated genes by decreasing bound STAT1 and Pol-II recruitment. Transcriptional suppression of ISGs requires conserved (L)LxxL(L) motifs in the carboxyterminal region of DUX4 and phosphorylation of STAT1 Y701 enhances interaction with DUX4. Consistent with these findings, expression of endogenous DUX4 in FSHD muscle cells and the CIC-DUX4 fusion containing the DUX4 CTD in a sarcoma cell line inhibit IFNγ-induction of ISGs. Mouse Dux similarly interacted with STAT1 and suppressed IFNγ induction of ISGs. These findings identify an evolved role of the DUXC family in modulating immune signaling pathways with implications for development, cancers, and FSHD.
From proteins to nanoparticles: domain-agnostic predictions of nanoscale interactions
Authors: Saldinger Jacob , Raymond Matt , Elvati Paolo , Violi Angela
Published: August 2022

The accurate and rapid prediction of generic nanoscale interactions is a challenging problem with broad applications. Much of biology functions at the nanoscale, and our ability to manipulate materials and engage biological machinery in a purposeful manner requires knowledge of nano-bio interfaces. While several protein-protein interaction models are available, they leverage protein-specific information, limiting their abstraction to other structures. Here, we present NeCLAS, a general, and rapid machine learning pipeline that predicts the location of nanoscale interactions, providing human-intelligible predictions. Two key aspects distinguish NeCLAS: coarsegrained representations, and the use of environmental features to encode the chemical neighborhood. We showcase NeCLAS with challenges for protein-protein, protein-nanoparticle and nanoparticle-nanoparticle systems, demonstrating that NeCLAS replicates computationally- and experimentally-observed interactions. NeCLAS outperforms current nanoscale prediction models and it shows cross-domain validity. We anticipate that our framework will contribute to both basic research and rapid prototyping and design of diverse nanostructures in nanobiotechnology.
Multimodal Image Normalisation Tool (MINT) for the Adolescent Brain and Cognitive Development study: the MINT ABCD Atlas
Authors: Pecheva Diliana , Iversen John R , Palmer Clare E , Watts Richard , Jernigan Terry L , Hagler Donald J , Dale Anders M
Published: August 2022

The Adolescent Brain and Cognitive Development (ABCD) study aims to measure the trajectories of brain, cognitive, and emotional development. Cognitive and behavioural development during late childhood and adolescence have been associated with a myriad of microstructural and morphological alterations across the brain, as measured by magnetic resonance imaging (MRI). These associations may be strongly localised or spatially diffuse, therefore, it would be advantageous to analyse multimodal MRI data in concert, and across the whole brain. The ABCD study presents the unique challenge of integrating multimodal data from tens of thousands of scans at multiple timepoints, within a reasonable computation time. To address the need for a multimodal registration and atlas for the ABCD dataset, we present the synthesis of an ABCD atlas using the Multimodal Image Normalisation Tool (MINT). The MINT ABCD atlas was generated from baseline and two-year follow up imaging data using an iterative approach to synthesise a cohort-specific atlas from linear and nonlinear deformations of eleven channels of diffusion and structural MRI data. We evaluated the performance of MINT against two widely used methods and show that MINT achieves comparable alignment to current state-of-the-art multimodal registration, at a fraction of the computation time. To validate the use of the ABCD MINT atlas in whole brain, voxelwise analysis, we replicate and expand on previously published region-of-interest analysis between diffusion MRI-derived measures and body mass index (BMI). We also report novel association between BMI and brain morphology derived from the registration deformations. We present the ABCD MINT atlas as a publicly available resource to facilitate whole brain voxelwise analyses for the ABCD study.
Inflammatory bowel disease-associated gut commensals degrade components of the extracellular matrix
Authors: Porras Ana Maria , Zhou Hao , Shi Qiaojuan , Xiao Xieyue ,   JRI Live Cell Bank, Longman Randy , Brito Ilana Lauren
Published: August 2022

Extracellular matrix (ECM) remodeling has emerged as a key feature of inflammatory bowel disease (IBD), and ECM fragments have been proposed as markers of clinical disease severity. Recent studies report increased protease activity in the gut microbiota of IBD patients. Nonetheless, the relationship between gut microbiota and ECM remodeling has remained unexplored. We hypothesized that members of the human gut microbiome can degrade host ECM, and that bacteria-driven remodeling, in turn, can enhance colonic inflammation. Through a variety ofin vitroassays, we first confirmed that multiple bacterial species found in the human gut are capable of degrading specific ECM components. Clinical stool samples obtained from ulcerative colitis patients also exhibited higher levels of proteolytic activityin vitrocompared to those of their healthy counterparts. Furthermore, culture supernatants from bacteria species capable of degrading human ECM accelerated inflammation in a dextran sodium sulfate (DSS)-induced colitis. Finally, we identified several of the bacterial proteases and carbohydrate degrading enzymes (CAZymes) potentially responsible for ECM degradationin vitro. Some of these protease families and CAZymes were also found in increased abundance in a metagenomic cohort of IBD. These results demonstrate that some commensal bacteria in the gut are indeed capable of degrading components of human ECMin vitroand suggest this proteolytic activity may be involved in the progression of IBD. A better understanding of the relationship between nonpathogenic gut microbes, host ECM, and inflammation could be crucial to unravel some of the mechanisms underlying host-bacteria interactions in IBD and beyond.
Nutrition scores and MUAC of adult surgical orthopaedic inpatients at a teaching hospital in Lusaka province, Zambia
Authors: Miyoba Nixon , Ogada Irene
Published: August 2022

Background

Poor nutrition status among hospitalised patients has been shown to increase length of hospital stay, as well as contribute to increased morbidity and mortality. The purpose of the study was to evaluate the nutrition status of adult surgical orthopaedic patients attending a teaching hospital in Zambia.

Methods

This study adopted a hospital-based cross-sectional study design to collect data from 98 adult patients aged 18 - 64 years. A structured questionnaire, the Subjective Global Assessment (SGA) tool, mid-upper arm circumference (MUAC) tape were used to collect data during the study period of three months in 2015.

Results

The mean age of the patients was 36.4 plus or minus 9.44 years, while the mean length of hospital stay was 17.33 plus or minus 10.91 days. Nutrition-focused physical examination revealed that majority (89.8%) of the patients were of acceptable weight with no weight loss reported in 70.4% of the patients. Poor appetite was only reported by 10.2% of the patients. SGA findings suggest that most of the patients (79.6%) were well-nourished. The mean mid-upper arm circumference of the study participants during hospitalization was 25.09 plus or minus 2.85 cm. An association was found between length of hospital stay and mid-upper arm circumference of the patients (p<0.001).

Conclusion

Subjective Global Assessment has the potential to evaluate the nutrition status of surgical patients in resource-poor settings such as Zambia. However, the use of SGA should be supplemented by other tools such as MUAC which has the potential to screen for adult malnutrition in clinical settings with limited resources.
Genetic variation associated with relative resistance in teak (Tectona grandis L. f.) against the leaf skeletonizer, Eutectona machaeralis Walker
Authors: Vaishnav Vivek , Kulkarni Nitin , Ansari Shamim Akhtar , Rana Tikam Singh
Published: August 2022

Background

Photosynthesizing tissue of teak (Tectona grandis L. f.) foliage is damaged by a host-specific insect pest called leaf skeletonizer (Eutectona machaeralis Walker) that severely eclipses annual growth increment and carbon sequestration of natural populations and plantation of teak. Gene-assisted selection of relatively resistant teak clones may efficiently control the damage in the populations and plantations. The present investigation aimed to identify genetic variation associated with relative resistance in teak against the pest.

Method

The investigation was carried out on 106 teak plus tree clones assembled at the National Teak Germplasm Bank from the Indian meta-population of teak. Resistance data were obtained recording the ocular damage caused by the pest to teak accessions for four years. Genotyping of the teak accessions was performed with 21 co-dominant markers and marker-trait association mapping was performed confirming the genetic structure of the germplasm bank and linkage disequilibrium (LD) among the marker loci.

Results

The sampled teak accessions exhibited a low albeit highly admixed genetic structure (FST=0.07) and low level of LD (16.66%) among loci, making them suitable for high-resolution association analysis. A significant correlation (p≤0.01, R2=0.67) was obtained between intra-specific heterozygosity and the relative resistance against the pest. A marker locus CCoAMT-1 representing the enzyme caffeoyl-CoA O-methyltransferase of phenylpropanoid pathway was also found significantly (p≤0.05) associated with the relative resistance against the pest explaining 6.6% of the phenotypic variation (R2=0.066) through positive effect (0.57) on the trait.

Conclusions

The present work exhibited a significant correlation of intra-specific heterozygosity with relative resistance in teak against a pest. It is the first report on teak identifying genetic markers associated with relative resistance against the pest. The marker can be applied for the selection of resistant planting stock for breeding and commercial plantation.

Further investigation can be performed to understand the expression level polymorphism linked with the resistance applying next-generation sequencing approaches.