bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and risk factors of enteral nutrition intolerance in intensive care unit patients: a retrospective study
Authors: Yu Kunrong , Guo Na , Zhang Dingding , Xia Ying , Meng Yanling , Weng Li , Du Bin
Published: July 2022

Background:

Feeding intolerance (FI) among intensive care unit (ICU) patients undergoing early continuous enteral nutrition (EN) is related to poor outcomes. This study aimed to explore the prevalence and risk factors of FI in ICU patients.

Methods:

We retrospectively enrolled 1057 patients who received early continuous EN via a nasogastric tube between January 2014 and August 2019. The prevalence of FI during the first 7 days of ICU stay was calculated, and the risk factors were investigated using multivariate logistic regression analysis.

Results:

The prevalence of FI during the first 7 days of ICU stay was 10.95%. FI occurred in 159 of 1057 (15.04%) patients on ICU day 2, 114 of 977 (11.67%) patients on ICU day 3, and 86 of 715 (12.03%) patients on ICU day 7. Mechanical ventilation (MV) (odds ratio [OR]: 1.928, 95% confidence interval [CI]: 1.064–3.493, P = 0.03) was an independent risk factor for FI defined by a gastric residual volume (GRV) of 200 mL and/or vomiting, and acute renal failure (OR: 3.445, 95% CI: 1.115–10.707, P = 0.032) was an independent risk factor of FI defined by a GRV of 500 mL and/or vomiting. Continuous renal replacement therapy (CRRT) was an independent predictor regardless of the FI defined by a GRV of 200 mL (OR: 2.064, 95% CI: 1.233–3.456, P = 0.006) or 500 mL (OR: 6.199, 95% CI: 2.108–18.228, P = 0.001) in the ICU patients.

Conclusions:

FI occurs frequently in early ICU days, especially in patients receiving MV and CRRT. However, further investigation of a consensus definition of FI and risk factors is still warranted in future studies.
Evaluating the Feasibility of a Statewide Collaboration to Improve Cardiac Rehabilitation Participation
Authors: Thompson Michael P. , Yaser Jessica M. , Forrest Annemarie , Keteyian Steven J. , Sukul Devraj
Published: July 2022

Purpose:

Regional quality improvement collaboratives may provide one solution to improving cardiac rehabilitation (CR) participation through performance benchmarking and provider engagement. The objective of this study was to evaluate the feasibility of the Michigan Cardiac Rehab Network to improve CR participation.

Methods:

Multipayer claims data from the Michigan Value Collaborative were used to identify hospitals and CR facilities and assemble a multidisciplinary advisory group. Univariate analyses described participating hospital characteristics and hospital-level rates of CR performance across eligible conditions including enrollment within 1 yr, mean days to first CR visit, and mean number of CR visits within 1 yr. Three diverse CR facilities were chosen for virtual site visits to identify areas of success and barriers to improvement.

Results:

A total of 95 hospitals and 84 CR facilities were identified, with 48 hospitals (51%) providing interventional cardiology services and 33 (35%) providing cardiac surgical services. A 17-member multidisciplinary advisory group was assembled representing 13 institutions and diverse roles. Statewide CR enrollment across eligible admissions was 33.4%, with wide variation in CR performance measures across participating hospitals and eligible admissions. Virtual site visits revealed individual successes in improving CR participation but a variety of barriers to participation related to referrals, capacity and staffing constraints, and geographic and financial barriers.

Conclusions:

This study demonstrated the feasibility of creating a statewide collaboration of hospitals and CR facilities centered around the goal of equitably improving CR enrollment for all eligible patients in Michigan that is supported by a multidisciplinary advisory group and performance benchmarking.
Point-of-care ultrasonography-assisted nasogastric tube placement in the emergency department: a randomized controlled trial
Authors: Yaseen Mohd , Kumar Akshay , Bhoi Sanjeev , Sinha Tej Prakash , Jamshed Nayer , Aggarwal Praveen , Murmu Lakhi Ram , Ekka Meera
Published: July 2022

Background

The complications of a blind procedure for gastric tube placement are well documented. POCUS has been widely used to confirm the position of blindly inserted gastric tubes, and it does not prevent complications caused by the blind method. We performed a randomized controlled trial to compare gastric tube insertion with real-time oesophagus visualization using POCUS to the standard technique.

Objective

The primary goal of this study was to compare the accuracy of real-time POCUS-guided nasogastric tube (NGT) insertion and confirmation to that of the standard technique.

Methods

It was a prospective, parallel-group, open-label randomized controlled trial with a superiority design. All patients requiring NGT were screened for inclusion and exclusion criteria, and 120 patients were randomly assigned to one of two groups: POCUS (n = 60) or control (n = 60). Following the procedures, confirmatory chest radiographs were obtained in both groups.

Results

As per protocol, 118 patients were analyzed. In POCUS group, the oesophagus was visualized on POCUS in 56 of 58 patients (96.5%). In 55 of 58 cases (94.8%), an NGT was inserted in real time. Despite visualizing the oesophagus, we fail to insert the tube in one (1.8%). The oesophagus could not be seen on the scan in two cases (3.4%). Chest radiographs confirmed the tube in the stomach in 55 (98.2%). The chest radiograph revealed the tip of the NGT in the stomach in 52 of 60 (86.6%) patients. In seven cases (11.7%), we were unable to insert NGT. On a chest radiograph, one (1.6%) tip of the tube was seen in the right lung and was safely removed. The ultrasound-guided gastric tube insertion had a sensitivity of 96.5% (95% CI, 88–99.6%) and a positive predictive value (PPV) of 98.2% (95% CI, 98.1–98.3%). The conventional technique had 88% (95% CI, 77–95%) sensitivity and a PPV of 98% (95% CI, 97.9–98.2%).

Conclusion

POCUS enables real-time insertion of a gastric tube with high sensitivity, in a short time with high first-attempt success rate and limited passage-related complications. POCUS should be utilized for NGT insertion whenever expertise is available on the bedside.
Comparative performance of the different orthotopic urinary diversions
Authors: Sheybaee Moghaddam Farshad , Ghoreifi Alireza , Djaladat Hooman
Published: July 2022

Purpose of review

Majority of patients undergoing radical cystectomy are suitable for orthotopic urinary diversion. The effect of different techniques of neobladder reconstruction on early and long-term postoperative complications is still being determined. Additionally, it is unclear which type of neobladder provides the best patient satisfaction. The purpose of this article is to review the outcomes of different orthotopic urinary diversions following radical cystectomy.

Recent findings

Ileal neobladder is the preferred type of orthotopic urinary diversion following radical cystectomy. Hautmann and Studer, which are the most common orthotopic diversion techniques, provide daytime continence rate up to 87% and 92%, respectively. However, nighttime continence is achieved in about 50% of patients. High-level evidence supports the long-term safety of orthotopic neobladder in terms of renal function, even in patients with a glomerular filtration rate <60 ml/min. Sexual dysfunction is the only independent factor associated with poorer quality of life in these patients.

The best type of neobladder is still uncertain. However, Studer and Hautmann are the most commonly performed techniques that provide favorable short- and long-term outcomes.
Estimating the minimum antiretroviral adherence required for plasma HIV-1 RNA viral load suppression among people living with HIV who use unregulated drugs
Authors: Stover Sofia , Milloy M.-J. , Grant Cameron , Fairbairn Nadia , Socías M. Eugenia
Published: July 2022

Objectives:

Owing to advances in antiretroviral therapy (ART), we re-examined minimum ART adherence levels necessary to achieve sustained HIV-1 viral load (VL) suppression among people with HIV who use drugs (PHIV-PWUD).

Design and methods:

We used data from ACCESS, a community-recruited prospective cohort of PHIV-PWUD in Vancouver, Canada. We calculated adherence using the proportion of days of ART dispensed in the year before each VL measurement. We used generalized linear mixed-effects models to identify adherence- and ART regimen-related correlates of VL suppression (<200 copies/ml). We employed probit regression models and generated dose–response curves to estimate the minimum adherence level needed to produce VL suppression in 90% of measures, stratified by regimen and calendar-year.

Results:

Among 837 ART-exposed PHIV-PWUD recruited between 1996 and 2017, the overall estimated adherence level necessary to achieve 90% VL suppression was 93% (95% confidence interval [CI]: 90–96). This differed by regimen: 69% (95% CI: 45–92) for integrase inhibitor (INSTI)-, 96% (95% CI: 92–100) for boosted protease inhibitor (bPI)-, and 98% (95% CI: 91–100) for non-nucleoside reverse transcriptase inhibitor-based regimens. In multivariable analysis, INSTI-based regimens were positively associated with VL suppression (vs. bPIs), while un-boosted PIs and other regimens were negatively associated. We observed a decreasing temporal trend of estimated adherence necessary for 90% VL suppression, dropping to 64% (95% CI: 50–77) during 2016–2017.

Conclusion:

Although high levels of ART adherence were necessary to achieve consistent VL suppression, the minimum necessary adherence levels decreased over time. Overall, INSTI-based regimens performed the best, suggesting that they should be preferentially prescribed to PHIV-PWUD.
Diagnosis of Traumatic Bronchobiliary Fistula With Late 99mTc-Mebrofenin SPECT/CT
Authors: Sánchez-Vera Yazmín , Aguilera-Hernández Estrella , Cardoza-Ochoa David R. , González-Díaz Jorge Iván
Published: July 2022

Bronchobiliary fistula (BBF) represents a rare disorder; it consists of abnormal interconnection between the biliary tract and bronchial trees. A 22-year-old woman with persistent chest pain, jaundice, and biliptysis was referred for hepatobiliary scintigraphy under clinical suspicion of a BBF. Patient medical history was consistent with biliary tree reconstruction secondary to an iatrogenic injury during cholecystectomy 4 years ago. Previous complementary studies (CT and MR cholangiopancreatography) were equivocal for diagnosis. Planar dynamic images of hepatobiliary scintigraphy in the first hour were inconclusive. A 24-hour SPECT/CT was performed and confirmed the BBF in a minimally invasive way.
Incidental Findings of Coexisting Metastatic Pancreatic Cancer in Patients With Prostate Cancer on 18F–Prostate-Specific Membrane Antigen PET/CT
Authors: Lu Yang , Li Chun
Published: July 2022

A 79-year-old man with rising prostate-specific antigen of 3.2 ng/mL and diagnosis of metastatic castration-resistant prostate cancer received abiraterone and prednisone for treatment regarding prostate-specific membrane antigen (PSMA)–avid bone lesions on PET/CT. Four months later, a follow-up 18F-DCFPyL PET/CT demonstrated new and increased multifocal PSMA-avid osseous and liver lesions, whereas prostate-specific antigen was stabled at 3.1 ng/mL. Biopsy of liver lesion showed metastasis from a primary pancreatic acinar cell carcinoma. Retrospectively, PSMA-avid pancreatic body lesion was identified on both PSMA PET/CT scans. This case illustrated that any above background PSMA uptake in the pancreas warrants suspicion for malignancy.
Reducing Recovery Times in Outpatient Liver Biopsies
Authors: Kelly Lisa , Simon Peter , Nash Angela , Thompson Julie , Affronti Mary Lou
Published: July 2022

This project is aimed to identify whether recovery times could be reduced in patients undergoing an outpatient liver biopsy. Liver biopsies are typically performed in a hospital setting, and many facilities require patients to recover for multiple hours, sometimes ranging from 4 to 6 hours. This can discourage the patient from undergoing the biopsy. Multiple studies have examined recovery times and determined patients can safely recover and be discharged within 1–2 hours post-liver biopsy. In this retrospective review, the data of 60 outpatients who underwent a liver biopsy from June to December 2020 were analyzed. Analysis included comparing vital signs and symptoms at the 2-hour recovery period and 4-hour discharge time also to see whether there were any hospital admissions 1 week post-liver biopsy. Descriptive statistics were utilized for the data collected in this study. Results demonstrated that after 2 hours, 55 (91.7%) patients had vital signs within safe parameters, pain less than 5 on a 10-point pain scale and denied any other symptoms. The remaining five patients (8.3%) did not meet discharge criteria at the 2-hour mark because of pain greater than 5 on the pain scale yet were still discharged safely at the 4-hour mark.
Four Decades of Clinical Liver Transplantation Research: Results of a Comprehensive Bibliometric Analysis
Authors: Jiang Decan , Ji Tengfei , Liu Wenjia , Bednarsch Jan , Selzner Markus , Pratschke Johann , Lurje Georg , Cao Tiansheng , Brüggenwirth Isabel M.A. , Martins Paulo N. , Arke Lang Sven , Peter Neumann Ulf , Czigany Zoltan
Published: July 2022

Background.

Nearly 40 y have passed since the 1983 National Institutes of Health Consensus-Development-Conference, which has turned liver transplantation (LT) from a clinical experiment into a routine therapeutic modality. Since‚ clinical LT has changed substantially. We aimed to comprehensively analyze the publication trends in the most-cited top-notch literature in LT science over a 4-decade period.

Methods.

A total of 106 523 items were identified between January 1981 and May 2021 from the Web of Science Core Collection. The top 100 articles published were selected using 2 distinct citation-based strategies to minimize bias. Various bibliometric tools were used for data synthesis and visualization.

Results.

The citation count for the final dataset of the top 100 articles ranged from 251 to 4721. Most articles were published by US authors (n = 61). The most prolific institution was the University of Pittsburgh (n = 15). The highest number of articles was published in Annals of Surgery, Hepatology, and Transplantation; however, Hepatology publications resulted in the highest cumulative citation of 9668. Only 10% of the articles were classified as evidence level 1. Over 90% of first/last authors were male. Our data depict the evolution of research focus over 40 y. In part, a disproportional flow of citations was observed toward already well-cited articles. This might also project a slowed canonical progress, which was described in other fields of science.

Conclusions.

This study highlights key trends based on a large dataset of the most-cited articles over a 4-decade period. The present analysis not only provides an important cross-sectional and forward-looking guidance to clinicians, funding bodies, and researchers but also draws attention to important socio-academic or demographic aspects in LT.
Association between neutrophil to lymphocyte ratio and mood polarity in adolescents admitted to an inpatient psychiatric ward
Authors: Drapisz Adi , Avrahami Matan , Ben Dor David H. , Bustan Yael , Mekori–Domachevski Ehud , Weizman Abraham , Barzilay Ran
Published: July 2022

Inflammatory processes are associated with mood disorders, but data on pediatric patients are scarce. The aim of this study was to investigate a possible association between elevated neutrophil/lymphocyte ratio (NLR) – a marker of inflammation and mood polarity (manic/depressed) in adolescents, admitted between 2010 and 2015 due to a mood disorder episode and to an adolescent inpatient ward. Electronic medical records of 305 patients (aged 10–19 years, 60.6% males) admitted during the study period due to a mood disorder episode were reviewed. Of these, 63 were diagnosed with manic episodes and 242 with depressive episodes. Multivariate analyses were used to compare NLR between and within the two groups, covarying for age, sex, and antipsychotic use. NLR was significantly higher in the manic episode group compared with the depression one. Moreover, in inpatients with multiple hospitalizations, the NLR was higher during their manic episodes than that during their nonmanic states. These results suggest that, as has been reported in adults with bipolar disorder, inflammatory mechanisms may be involved in adolescents’ mood disorders as well, particularly in the manic episodes. Thus, clinicians may consider adding anti-inflammatories as part of the treatment of these patients.
Cervical Spinal Cord Modulation with Repeated Epidural Stimulation in Healthy Adult Rats
Authors: Sharma Pawan , Rampersaud Hema , Shah Prithvi K.
Published: July 2022

The effects of spinal epidural stimulation (ES) in regaining various physiological functions after a spinal cord injury (SCI) are well documented. Spinal evoked motor responses (SEMR) are commonly utilized experimental outcomes in longitudinal pre-clinical and human studies to reflect the in-vivo physiological changes in neural networks secondary to a neurological insult or neuro-rehabilitative treatments utilizing ES. However, it remains unknown if the repeated exposure to ES during SEMRs testing itself modulates the spinal cord physiology and hence the SEMRs characteristics. To address this issue, cervical ES was delivered to the healthy adult rat’s cervical cord using standard stimulation paradigms during multiple sessions (∼17 hours that spanned across 100 days). Cervical SEMR and electromyography (EMG) activity from forelimb muscles during a reaching & grasping task were collected before and after 100 days. We noted persistent increase in the cervical SEMR and forelimb muscle activity during reaching & grasping task relative to baseline at the end of the stimulation period indicating increased spinal and cortical excitability. Findings from the present work suggests that cervical SEMRs are amenable to modulation by routine ES testing protocols, with prominent changes in the mono and poly synaptic component of evoked responses. Additionally, since multiple testing sessions of cervical ES alone increases the excitability of the intact spinal cord, we suggest that SEMR data be used with caution to infer the physiological status of the spinal circuitry in longitudinal studies involving multiple SEMR testing sessions. Our findings also recommend involving appropriate control groups, motor behavior correlates, and practicing caution while utilizing normalization methods to allow meaningful functional interpretation of SEMR profiles following a SCI.
Estimating the genome-wide mutation rate from thousands of unrelated individuals
Authors: Tian Xiaowen , Cai Ruoyi , Browning Sharon R.
Published: July 2022

We provide a method for estimating the genome-wide mutation rate from sequence data on unrelated individuals by using segments of identity by descent (IBD). The length of an IBD segment indicates the time to shared ancestor of the segment, and mutations that have occurred since the shared ancestor result in discordances between the two IBD haplotypes. Previous methods for IBD-based estimation of mutation rate have required the use of family data in order to accurately phase the genotypes. This has limited the scope of application of IBD-based mutation rate estimation. Here, we develop an IBD-based method for mutation rate estimation from population data, and we apply it to whole genome sequence data on 4,166 European American individuals from the TOPMed Framingham Heart Study, 2,966 European American individuals from the TOPMed My Life Our Future study, and 1,586 African American individuals from the TOPMed Hypertension Genetic Epidemiology Network study. Although mutation rates may differ between populations due to genetic factors, demographic factors such as average parental age, and environmental exposures, our results are consistent with equal genome-wide average mutation rates across these three populations. Our overall estimate of the average genome-wide mutation rate per 108 base pairs per generation for single nucleotide variants is 1.24 (95% CI 1.18-1.33).
Identification of a distinct ductal subpopulation with self-renewal and differentiation potential from the adult murine pancreas
Authors: Tremblay Jacob R. , Ortiz Jose , Quijano Janine C. , Zook Heather , LeBon Jeanne M. , Li Wendong , Jou Kevin , Tsark Walter , Mann Jeffrey R. , Kozlowski Mark , Tirrell David A. , Esni Farzad , Engle Dannielle D. , Riggs Arthur D. , Ku Hsun Teresa
Published: July 2022

Pancreatic ducts function to deliver digestive enzymes into the intestines. Upon injury, ducts can become proliferative and contribute to tissue regeneration; however, the identity of the ductal cells that contribute to these processes is unknown. We combined fluorescence-activated cell sorting, a methylcellulose-containing 3-dimensional culture, droplet RNA-sequencing, and a clonal lineage tracing tool to identify and isolate a distinct subpopulation of pancreatic ductal cells that exhibit progenitor cell properties. These ductal cells are unique in that they form tightly-bound clusters (termed FSCmid-high), with an average of 8 cells per cluster. FSCmid-high clusters comprise only about 0.1% of the total pancreas, are tri-potent for duct, acinar and endocrine lineages, and self-renew robustly in vitro. Transcriptomic analysis of FSCmid-high clusters reveals enrichment for genes involved in cell-cell interactions, organ development, and cancer pathways. FSCmid-high clusters express embryonic pancreatic progenitor markers Sox9, Pdx1, and Nkx6-1 at both transcription and protein levels. FSCmid-high clusters are resistant to enzymatic dissociation and survive severe in vivo acinar injury, which induces formation of ductal rosettes that become proliferative within 14 days. Thus, FSCmid-high clusters represent a small subset of ductal cells with progenitor cell properties. These rare progenitor-like duct cell clusters have implications in pancreas regeneration and tumor initiation/progression.
Identification of leukemia-associated immunophenotypes by database-guided flow cytometry provides a highly sensitive and reproducible strategy for the study of measurable residual disease in acute myeloblastic leukemia
Authors: Pinero P , Morillas M , Gutiérrez N , Barragán E , Such E , Breña J , Gil C , García C , Botella C , Navajas JM , Zapater P , Montesinos P , Sempere A , Tarín F
Published: July 2022

Background

Multiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD).

Methods

In this study, we identified and characterized LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with 6 databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML.

The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCR-MRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS).

Results

The strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS.

Conclusions

The described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.
Environmental fluctuations explain the universal decay of species-abundance correlations with phylogenetic distance
Authors: Sireci Matteo , Muñoz Miguel A. , Grilli Jacopo
Published: July 2022

Multiple ecological forces act together to shape the composition of microbial communities.Phyloecologyapproaches —which combine phylogenetic relationships with community ecology— have the potential to disentangle such forces, but are often hard to connect with quantitative predictions from theoretical models. On the other hand,macroecology, which focuses on statistical patterns of abundance and diversity, provides natural connections with theoretical models but often neglects inter-speficic correlations and interactions. Here, we propose a unified framework combining both such approaches to analyze microbial communities. In particular, by using both cross-sectional and longitudinal metagenomic data for species abundances, we reveal the existence of a novel empirical macroecological law establishing that correlations in species-abundance fluctuations across communities decay from positive to null values as a function of phylogenetic similarity in a consistent manner across ecologically distinct microbiomes. We formulate three mechanistic models —relying on alternative ecological forces— that lead to radically different predictions. We conclude that the empirically observed macroecological pattern can be quantitatively explained as a result of shared fluctuating resources, i.e.environmental filteringand not e.g. as a consequence of species competition. Finally, we also show that the macroecological law is also valid for temporal data of a single community, and that the properties of delayed temporal correlations are reproduced by the model with environmental filtering.
Circadian regulation of hippocampal function is disrupted with chronic corticosteroid treatment
Authors: Birnie Matthew T. , Claydon Matthew D.B. , Flynn Benjamin P. , Yoshimura Mitsuhiro , Kershaw Yvonne M. , Demski-Allen Rebecca C.R. , Barker Gareth R.I. , Warburton E. Clea , Bortolotto Zuner A. , Lightman Stafford L. , Conway-Campbell Becky L.
Published: July 2022

Neuropsychiatric disorders such as major depression and schizophrenia are highly prevalent and contribute substantially to disease burden worldwide. Despite this, progress understanding the pathophysiology has remained largely elusive, yet these disorders often exhibit a loss of regulation of biological rhythms, such as sleep/wake cycles and hormonal rhythms. Cushing’s disease, a condition characterized by chronic corticosteroid (cortisol) hypersecretion is associated with psychiatric and neurocognitive disorders and disruption to the circadian release of cortisol can result in depression and neurocognitive impairment. In rats, we report that circadian regulation of the hippocampal transcriptome integrates crucial functional networks that link corticosteroid-inducible gene regulation to synaptic plasticity regulation via an intra-hippocampal circadian transcriptional clock. During the early active period, when corticosteroid availability is high, CA1 region excitatory and inhibitory post-synaptic currents were augmented along with long-term potentiation. In contrast, chronic corticosteroid exposure disturbed hippocampal function. The hippocampal transcriptome, as well as circadian regulation of synaptic plasticity were ablated, resulting in memory loss during hippocampal-dependent behavior. These findings identify how exposure to elevated levels of corticosteroid, that is often seen in neuropsychiatric illness, results in adverse critical hippocampal function. These data provide novel insights into the molecular mechanisms of neurocognitive disorders and provides evidence for corticosteroid-mediated intervention in disabling mental illnesses.
Tex2 is required for lysosomal functions at TMEM55-dependent ER membrane contact sites
Authors: Du Yuanjiao , Chang Weiping , Deng Lin , Ji Wei-Ke
Published: July 2022

ER tubules form and maintain membrane contact sites (MCSs) with late endosomes/lysosomes (LE/lys). The molecular composition and cellular functions of these MCSs are poorly understood. Here we find that Tex2, an SMP domain-containing lipid transfer protein conserved in metazoen and yeast, is a tubular ER protein, and enriches at ER-LE/lys MCSs dependent on TMEM55, phosphatases that convert PI(4,5)P2 to PI5P on LE/lys. We show that the Tex2-TMEM55 interaction occurs between a N-terminal region of Tex2 and a catalytic motif in PTase domain of TMEM55. The Tex2-TMEM55 interaction can be regulated by endosome-resident type 2 PI4K activities. Functionally, Tex2 knockout results in severe defects in lysosomal digestive capacity and blocked autophagic flow, as well as an aberrant accumulation of PI3P on the LE/lys membranes. These defects can be substantially rescued by wild type Tex2 other than a lipid transfer-defective Tex2 mutant, indicating an important role of lipid transfer in these processes. Together our data identify Tex2 as a tubular ER protein that resides at TMEM55-depedent ER-LE/lys MCSs required for lysosomal functions.
Neural Distinctiveness and Reinstatement of Hippocampal Representations Support Unitization for Associations
Authors: Ricupero S. , Carpenter C.M. , Steinkrauss A.C. , Gerver C.R. , Chamberlain J.D. , Monkman R.G. , Overman A.A. , Dennis N.A.
Published: July 2022

The medial temporal lobe (MTL) is critical to associative memory success. Yet not all types of associations may be processed in a similar manner within MTL subregions. In particular, work suggests that intra- and inter-item associations not only exhibit differences in overall rates of recollection, but also recruit different MTL subregions. Whereas intra-item associations, akin to unitization, take advantage of associations between within-item features, inter-item associations form links across discrete items. The current work aimed to examine the neural differences between these two types of associations using multivariate neural analyses. Specifically, the current study examined differences across face-occupation as a function of whether the pairing was viewed as a person performing the given job (intra-item binding) or a person saying that they knew someone who had a particular job (inter-item binding). The results show that at encoding, successfully recollected intra- and inter-item associations are discriminable from one another in the hippocampus, parahippocampal cortex, and perirhinal cortex. Additionally, the two trial types are reinstated distinctly such that inter-item trials have higher neural reinstatement from encoding to retrieval compared to intra-item trials in the hippocampus. We conclude that intra- and inter-associative pairs may utilize similar neural regions that represent patterns of activation differentially at encoding. However, in order to reinstate information to the same degree (i.e., subsequently successfully recollected) inter-item associations may act in a compensatory manner, while it is not necessary for intra-item associations to be reinstated to the same degree. This may indicate that intra-item associations promote more efficient reinstatement.
Structural basis of interdomain communication in PPARγ
Authors: Mosure Sarah A. , Munoz-Tello Paola , Kuo Kuang-Ting , MacTavish Brian , Yu Xiaoyu , Scholl Daniel , Williams Christopher C. , Strutzenberg Timothy S. , Li Jess , Bass Jared , Brust Richard , Kalkhoven Eric , Deniz Ashok A. , Griffin Patrick R. , Kojetin Douglas
Published: July 2022

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) regulates transcription via two activation function (AF) regulatory domains: a ligand-dependent AF-2 coregulator interaction surface within the C-terminal ligand-binding domain (LBD), and an N-terminal disordered AF-1 domain (NTD or A/B region) that functions through poorly understood structural mechanisms. Here, we show the PPARγ AF-1 contains an evolutionary conserved Trp-Pro motif that undergoes cis/trans isomerization, populating two long-lived conformations that participate in intradomain AF-1 and interdomain interactions including two surfaces in the C-terminal LBD (β-sheet and the AF-2 surface), which are predicted in AlphaFold 3 models but not AlphaFold 2. NMR and chemical crosslinking mass spectrometry show that interdomain interactions occur for soluble isolated AF-1 and LBD proteins, as well as in full-length PPARγ in a phase separated state. Mutation of the region containing the Trp-Pro motif, which abrogates cis/trans isomerization of this region, impacts LBD interaction and reduces basal PPARγ transcription and agonist-dependent activation of PPARγ. Our findings provide structural insight into published in vitro and cellular studies that reported interdomain functional communication between the PPARγ AF-1 and LBD suggesting some of these effects may be mediated via AF-1/LBD interactions.
MukBEF-dependent chromosomal organization in widened Escherichia coli
Authors: Japaridze Aleksandre , van Wee Raman , Gogou Christos , Kerssemakers Jacob W. J. , Dekker Cees
Published: July 2022

The bacterial chromosome is spatially organized through protein-mediated compaction, supercoiling, and cell-boundary confinement. Structural Maintenance of Chromosomes (SMC) complexes are a major class of chromosome-organizing proteins present throughout all domains of life. Here, we study the role of the Escherichia coli SMC complex MukBEF in chromosome architecture and segregation. Using quantitative live-cell imaging of shape-manipulated cells, we show that MukBEF is crucial to preserve the toroidal topology of the E. coli chromosome and that it is non-uniformly distributed along the chromosome: it prefers locations towards the origin and away from the terminus of replication, and it is unevenly distributed over the origin of replication along the two chromosome arms. Using an ATP hydrolysis-deficient MukB mutant, we find that MukBEF translocation along the chromosome is ATP-dependent, in contrast to its loading onto DNA. MukBEF and MatP are furthermore found to be essential for sister chromosome decatenation. We propose a model that explains how MukBEF, MatP, and their interacting partners organize the chromosome and contribute to sister segregation and recombination. The combination of bacterial cell-shape modification and quantitative fluorescence microscopy paves way to investigating chromosome-organization factors in vivo.
Kindlin-2 inhibits TNF/NF-κB-caspase 8 pathway in hepatocytes to maintain liver development and function
Authors: Gao Huanqing , Zhong Yiming , Zhou Liang , Lin Sixiong , Hou Xiaoting , Ding Zhen , Li Yan , Yao Qing , Cao Huiling , Zou Xuenong , Chen Di , Bai Xiaochun , Xiao Guozhi
Published: July 2022

Inflammatory liver diseases are a major cause of morbidity and mortality worldwide; however, underlying mechanisms are incompletely understood. Here we show that deleting the focal adhesion protein Kindlin-2 in hepatocytes using the Alb-Cre transgenic mice causes a severe inflammation, resulting in premature death. Kindlin-2 loss accelerates hepatocyte apoptosis with subsequent compensatory cell proliferation and accumulation of the collagenous extracellular matrix, leading to massive liver fibrosis and dysfunction. Mechanistically, Kindlin-2 loss abnormally activates the tumor necrosis factor (TNF) pathway. Blocking activation of the TNF signaling pathway by deleting TNF receptor or deletion of caspase 8 expression in hepatocytes essentially restores liver function and prevents premature death caused by Kindlin-2 loss.Finally, of translational significance, adeno-associated virus mediated overexpression of Kindlin-2 in hepatocytes attenuates the D-galactosamine and lipopolysaccharide-induced liver injury and death in mice. Collectively, we establish that Kindlin-2 acts as a novel intrinsic inhibitor of the TNF pathway to maintain liver homeostasis and may define a useful therapeutic target for liver diseases.
ExTrack characterizes transition kinetics and diffusion in noisy single-particle tracks
Authors: Simon Francois , Tinevez Jean-Yves , van Teeffelen Sven
Published: July 2022

Single-particle tracking microscopy is a powerful technique to investigate how proteins dynamically interact with their environment in live cells. However, the analysis of tracks is confounded by noisy molecule localization, short tracks, and rapid transitions between different motion states, notably between immobile and diffusive states. Here, we propose a probabilistic method termed ExTrack that uses the full spatio-temporal information of tracks to extract global model parameters, to calculate state probabilities at every time point, to reveal distributions of state durations, and to refine the positions of bound molecules. ExTrack works for a wide range of diffusion coefficients and transition rates, even if experimental data deviate from model assumptions. We demonstrate its capacity by applying it to slowly diffusing and rapidly transitioning bacterial envelope proteins. ExTrack greatly increases the regime of computationally analyzable noisy single-particle tracks. The ExTrack package is available in ImageJ and Python.
Newborn chicks prefer stimuli that move against gravity
Authors: Bliss Larry , Vasas Vera , Freeland Laura , Roach Robyn , Ferrè Elisa Raffaella , Versace Elisabetta
Published: July 2022

At the beginning of life, inexperienced animals use evolutionary-given preferences (predispositions) to decide what stimuli attend and approach. Stimuli that contain cues of animacy, such as face-like stimuli, biological motion and changes in speed, are particularly attractive across vertebrate taxa. A strong cue of animacy is upward movement against terrestrial gravity, because only animate objects consistently move upward. To test whether upward movement is spontaneously considered attractive already at birth, we tested the early preferences of dark-hatched chicks (Gallus gallus) for upward vs downward moving visual stimuli. We found that, without any previous visual experience, chicks consistently exhibited a preference to approach upward moving stimuli, that move against gravity. A control experiment showed that these preferences are not driven by avoidance of downward stimuli. These results show that newborn animals are spontaneously attracted by upward movement, indicating that movement against gravity can be used as a cue of animacy to orient early approach responses in the absence of previous visual experience.
Modeling congenital heart disease: lessons from mice, hPSC-based models, and organoids
Authors: Rao Kavitha S. , Kameswaran Vasumathi , Bruneau Benoit G.
Published: July 2022

Congenital heart defects (CHDs) are among the most common birth defects, but their etiology has long been mysterious. In recent decades, the development of a variety of experimental models has led to a greater understanding of the molecular basis of CHDs. In this review, we contrast mouse models of CHD, which maintain the anatomical arrangement of the heart, and human cellular models of CHD, which are more likely to capture human-specific biology but lack anatomical structure. We also discuss the recent development of cardiac organoids, which are a promising step toward more anatomically informative human models of CHD.
Subgroup-specific roles of primary cilia in medulloblastoma
Authors: Marino Silvia
Published: July 2022

Here I discuss the study in this issue of Genes & Development by Youn et al. (pp. 737–751), which describes defined and diverse roles of primary cilia in molecularly distinct medulloblastoma subgroups, highlighting once again the importance of designing subgroup-specific therapeutic approaches for this tumor.
Crystal structure, Hirshfeld surface and frontier molecular orbital analysis of 10-benzyl-9-(4-hydroxy-3-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
Authors: Sughanya V. , Loganathan B. , Praveenkumar D. , Ayyappan J. , Sundararajan M. L. , Prabhakaran A. , Dhandapani A. , Suresh Babu N.
Published: July 2022

In the fused ring system of the title molecule, C31H35NO4, the conformation of the central dihydropyridine ring is intermediate between boat and envelope with the N and the opposite C atoms lying out of the basal plane. The conformations of terminal rings are close to envelope, with the atoms substituted by two methyl groups as the flaps. In the crystal, the molecules are linked by O—H...O hydrogen bonds into helical chains. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (63.2%), O...H/H...O (20.1%) and C...H/H...C (14.4%) contacts. Quantum chemical calculations of the frontier molecular orbitals were carried out to characterize the chemical reactivity of the title compound.
Gaps in megaproject management system literature: a systematic overview
Authors: Ashkanani Salman , Franzoi Robert
Published: July 2022

Purpose

This paper aims to present a structured and comprehensive review of relevant works, collected through a systematic methodology and clustered into nine meaningful categories on megaproject management systems and the current requirements for improved industrial megaprojects.

Design/methodology/approach

The methodology employed in this paper retrieves relevant works from available online citation indexes that are published in peer-reviewed journals and other reliable sources from 2000 to 2021.

Findings

It has been observed that the literature on megaproject management is still premature and requires further research to understand better the main gaps and effects of large-scale and typically complex megaprojects. Significant improvements are needed towards covering gaps to address the project management system holistically over the entire project life cycle. There are no clear guidelines for achieving a complete and conclusive project management system and enhancing future megaprojects' management capabilities.

Originality/value

This paper provides a clear picture of the existing literature on megaproject management systems, contributing insights for successful megaproject projects. Additionally, the holistic analysis identifies gaps in the body of knowledge, revealing avenues for future research.
Entrepreneurial mentoring, financial support and incubator patent licensing: evidence from Chinese incubators
Authors: Chang Yanru , Cheng Qiang
Published: July 2022

Purpose

Based on Chinese incubators as the research sample, this paper aims to examine whether and how incubators' entrepreneurial mentoring and financial support affect incubator patent licensing. Entrepreneurial mentoring functions through the buffering mechanism and financial support functions through the bridging and curating mechanisms.

Design/methodology/approach

A negative binomial model is used to empirically explain the relation between entrepreneurial mentoring or financial support and incubator patent licensing. In addition, a cross-sectional test is performed to explore whether province-level incubator support policies strengthen the effect of entrepreneurial mentoring and financial support on incubator patent licensing.

Findings

The results reveal that incubators' entrepreneurial mentoring positively affects patent licensing. In contrast, incubators' financial support has an inverted U-shaped relationship with patent licensing. In addition, the two relations are stronger when an incubator locates in a province with more incubator support policies.

Originality/value

The authors contribute to the literature on incubator performance by identifying an important but less discussed factor: entrepreneurial mentoring. Through the connection with mentors, tenants efficiently commercialize the value of their patents, facilitate patent licensing and expand the product market. Furthermore, the inverted U-shaped association between financial support and patent licensing shows that incubation support does not always have a linear effect on incubator patent licensing. Overall, this study provides evidence on the effect of incubator support on incubator patent licensing.
An analysis of climate change and health hazards: results from an international study
Authors: Leal Filho Walter , Ternova Linda , Fayyaz Muhammad Muddassir , Abubakar Ismaila Rimi , Kovaleva Marina , Donkor Felix Kwabena , Anuga Samuel Weniga , Matamanda Abraham R. , Djekic Ilija , Umar Ibrahim Abatcha , Olooto Felicia Motunrayo , Meirelles Maria , Nagy Gustavo J. , May Julia , May Marta , Ebhuoma Eromose , Begum Halima
Published: July 2022

Purpose

The interconnections between climate change and health are well studied. However, there is a perceived need for studies that examine how responses to health hazards (e.g. cardiovascular diseases, ozone layer effects, allergens, mental health and vector-borne diseases) may assist in reducing their impacts. The purpose of this paper is to review the evidence on health responses to climate hazards and list some measures to address them.

Design/methodology/approach

A mixed literature review, bibliometric analysis and an original online survey were undertaken on 140 participants from 55 countries spread across all geographical regions.

Findings

The bibliometric analysis identified that most climate-related health hazards are associated with extreme weather events. However, only one-third of the investigated papers specifically analysed the connections between climate change and health hazards, revealing a thematic gap. Also, although Africa is highly affected by climate change, only 5% of the assessed studies focused on this continent. Many respondents to the survey indicated “heat distress” as a significant vulnerability. The survey also identified social determinants relevant to climate-induced health vulnerabilities, such as socioeconomic and environmental factors, infrastructure and pre-existing health conditions. Most respondents agree that policies and regulations are the most effective adaptation tools to address the public health hazards triggered by climate change. This paper presents some suggestions for optimising public health responses to health hazards associated with climate change, such as the inclusion of climate-related components in public health policies, setting up monitoring systems to assess the extent to which specific climate events may pose a health threat, establishing plans to cope with the health implications of heatwaves, increased measures to protect vulnerable groups and education and awareness-raising initiatives to reduce the overall vulnerability of the population to climate-related health hazards. These measures may assist the ongoing global efforts to understand better – and cope with – the impacts of climate change on health.

Originality/value

The combination of a literature review, bibliometric analysis and an original world survey identified and presented a wide range of responses.