bluuebunny/crossref_metadata_2025 huggingface dataset:
Npl3 functions in mRNP assembly by recruitment of mRNP components to the transcription site and their transfer onto the mRNA
Authors: Keil Philipp , Wulf Alexander , Kachariya Nitin , Reuscher Samira , Hühn Kristin , Silbern Ivan , Altmüller Janine , Keller Mario , Stehle Ralf , Zarnack Kathi , Sattler Michael , Urlaub Henning , Sträßer Katja
Published: December 2022

RNA-binding proteins (RBPs) control every RNA metabolic process by multiple protein–RNA and protein–protein interactions. Their roles have largely been analyzed by crude mutations, which abrogate multiple functions at once and likely impact the structural integrity of the large ribonucleoprotein particles (RNPs) these proteins function in. Using UV-induced RNA–protein crosslinking of entire cells, protein complex purification and mass spectrometric analysis, we identified >100 in vivo RNA crosslinks in 16 nuclear mRNP components in Saccharomyces cerevisiae. For functional analysis, we chose Npl3, which displayed crosslinks in its two RNA recognition motifs (RRMs) and in the connecting flexible linker region. Both RRM domains and the linker uniquely contribute to RNA recognition as revealed by NMR and structural analyses. Interestingly, mutations in these regions cause different phenotypes, indicating distinct functions of the different RNA-binding domains. Notably, an npl3-Linker mutation strongly impairs recruitment of several mRNP components to chromatin and incorporation of other mRNP components into nuclear mRNPs, establishing a so far unknown function of Npl3 in nuclear mRNP assembly. Taken together, our integrative analysis uncovers a specific function of the RNA-binding activity of the nuclear mRNP component Npl3. This approach can be readily applied to RBPs in any RNA metabolic process.
Ratchet, swivel, tilt and roll: a complete description of subunit rotation in the ribosome
Authors: Hassan Asem , Byju Sandra , Freitas Frederico Campos , Roc Claude , Pender Nisaa , Nguyen Kien , Kimbrough Evelyn M , Mattingly Jacob M , Gonzalez Jr. Ruben L , de Oliveira Ronaldo Junio , Dunham Christine M , Whitford Paul C
Published: December 2022

Protein synthesis by the ribosome requires large-scale rearrangements of the ‘small’ subunit (SSU; ∼1 MDa), including inter- and intra-subunit rotational motions. However, with nearly 2000 structures of ribosomes and ribosomal subunits now publicly available, it is exceedingly difficult to design experiments based on analysis of all known rotation states. To overcome this, we developed an approach where the orientation of each SSU head and body is described in terms of three angular coordinates (rotation, tilt and tilt direction) and a single translation. By considering the entire RCSB PDB database, we describe 1208 fully-assembled ribosome complexes and 334 isolated small subunits, which span >50 species. This reveals aspects of subunit rearrangements that are universal, and others that are organism/domain-specific. For example, we show that tilt-like rearrangements of the SSU body (i.e. ‘rolling’) are pervasive in both prokaryotic and eukaryotic (cytosolic and mitochondrial) ribosomes. As another example, domain orientations associated with frameshifting in bacteria are similar to those found in eukaryotic ribosomes. Together, this study establishes a common foundation with which structural, simulation, single-molecule and biochemical efforts can more precisely interrogate the dynamics of this prototypical molecular machine.
Kinetics of elementary steps in loop-mediated isothermal amplification (LAMP) show that strand invasion during initiation is rate-limiting
Authors: Dangerfield Tyler L , Paik Inyup , Bhadra Sanchita , Johnson Kenneth A , Ellington Andrew D
Published: December 2022

Loop-mediated isothermal amplification (LAMP) has proven to be easier to implement than PCR for point-of-care diagnostic tests. However, the underlying mechanism of LAMP is complicated and the kinetics of the major steps in LAMP have not been fully elucidated, which prevents rational improvements in assay development. Here we present our work to characterize the kinetics of the elementary steps in LAMP and show that: (i) strand invasion / initiation is the rate-limiting step in the LAMP reaction; (ii) the loop primer plays an important role in accelerating the rate of initiation and does not function solely during the exponential amplification phase and (iii) strand displacement synthesis by Bst-LF polymerase is relatively fast (125 nt/s) and processive on both linear and hairpin templates, although with some interruptions on high GC content templates. Building on these data, we were able to develop a kinetic model that relates the individual kinetic experiments to the bulk LAMP reaction. The assays developed here provide important insights into the mechanism of LAMP, and the overall model should be crucial in engineering more sensitive and faster LAMP reactions. The kinetic methods we employ should likely prove useful with other isothermal DNA amplification methods.
Psychosocial risk in healthcare workers after one year of COVID-19
Authors: Moreno Martínez M , Feijoo-Cid M , Fernández-Cano M I , Llorens-Serrano C , Navarro-Giné A
Published: December 2022

Background

The COVID-19 pandemic overwhelmed the capacity of the healthcare system, affecting the volume of demands and the care tasks of healthcare workers.

Aims

To examine the health indicators and exposure to psychosocial risks of Spanish healthcare workers 1 year into the COVID-19 pandemic and compare them with the results of the first wave.

Methods

We conducted a cross-sectional study using an online questionnaire (April–May 2020 and 2021). The data stem from the COTS 1 project database, corresponding to the first wave of COVID-19 (n = 1989) and COTS 2 (n = 1716) corresponding to 1 year later. The samples were independent. The prevalence of exposure to psychosocial risks and adverse health indicators was estimated for every occupational group, segregating the data by sex.

Results

Professionals of all types presented worse perception of health. In general, the results were worse for women, while geriatric assistants presented the greatest exposure to psychosocial risk in COTS 2 compared to COTS 1. Sleep problems, high quantitative demands and high concern about becoming infected and spreading COVID-19 were cross-disciplinary in COTS 1, while worse perception of health, high pace of work, high work–life conflict and low development opportunities stood out in COTS 2.

Conclusions

Exposure to psychosocial risks was already high during the first wave and a significant decline in working conditions was observed. The prolongation of the pandemic exacerbated these results and seems to have multiplied the pre-existing inequalities between the axes of segregation in the labour market.
Organelle-targeted biosensors reveal distinct oxidative events during pattern-triggered immune responses
Authors: Arnaud Dominique , Deeks Michael J , Smirnoff Nicholas
Published: December 2022

Reactive oxygen species are produced in response to pathogens and pathogen-associated molecular patterns, as exemplified by the rapid extracellular oxidative burst dependent on the NADPH oxidase isoform RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) in Arabidopsis (Arabidopsis thaliana). We used the H2O2 biosensor roGFP2-Orp1 and the glutathione redox state biosensor GRX1-roGFP2 targeted to various organelles to reveal unsuspected oxidative events during the pattern-triggered immune response to flagellin (flg22) and after inoculation with Pseudomonas syringae. roGFP2-Orp1 was oxidized in a biphasic manner 1 and 6 h after treatment, with a more intense and faster response in the cytosol compared to chloroplasts, mitochondria, and peroxisomes. Peroxisomal and cytosolic GRX1-roGFP2 were also oxidized in a biphasic manner. Interestingly, our results suggested that bacterial effectors partially suppress the second phase of roGFP2-Orp1 oxidation in the cytosol. Pharmacological and genetic analyses indicated that the pathogen-associated molecular pattern-induced cytosolic oxidation required the BRI1-ASSOCIATED RECEPTOR KINASE (BAK1) and BOTRYTIS-INDUCED KINASE 1 (BIK1) signaling components involved in the immune response but was largely independent of NADPH oxidases RBOHD and RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF) and apoplastic peroxidases peroxidase 33 (PRX33) and peroxidase 34 (PRX34). The initial apoplastic oxidative burst measured with luminol was followed by a second oxidation burst, both of which preceded the two waves of cytosolic oxidation. In contrast to the cytosolic oxidation, these bursts were RBOHD-dependent. Our results reveal complex oxidative sources and dynamics during the pattern-triggered immune response, including that cytosolic oxidation is largely independent of the preceding extracellular oxidation events.
Specific suppression of long terminal repeat retrotransposon mobilization in plants
Authors: Brestovitsky Anna , Iwasaki Mayumi , Cho Jungnam , Adulyanukosol Natthawut , Paszkowski Jerzy , Catoni Marco
Published: December 2022

The tissue culture passage necessary for the generation of transgenic plants induces genome instability. This instability predominantly involves the uncontrolled mobilization of LTR retrotransposons (LTR-TEs), which are the most abundant class of mobile genetic elements in plant genomes. Here, we demonstrate that in conditions inductive for high LTR-TE mobilization, like abiotic stress in Arabidopsis (Arabidopsis thaliana) and callus culture in rice (Oryza sativa), application of the reverse transcriptase (RT) inhibitor known as Tenofovir substantially affects LTR-TE RT activity without interfering with plant development. We observed that Tenofovir reduces extrachromosomal DNA accumulation and prevents new genomic integrations of the active LTR-TE ONSEN in heat-stressed Arabidopsis seedlings, and transposons of O. sativa 17 and 19 (Tos17 and Tos19) in rice calli. In addition, Tenofovir allows the recovery of plants free from new LTR-TE insertions. We propose the use of Tenofovir as a tool for studies of LTR-TE transposition and for limiting genetic instabilities of plants derived from tissue culture.
Pediatric traumatic brain injury in a high-income developing country: experience at a level 1 neuro-trauma center
Authors: Al-Busaidi Fatma , Allawati Moosa , Al-Araimi Maryam Al-Fannah , Alhosni Asma , Al-Jubouri Yasir , Al-Mufargi Younis , Ali Mohammed , Al-Saadi Hatem , Al-Saadi Tariq
Published: December 2022

Background

Data on the incidence, prevalence and mortality of pediatric traumatic brain injuries (TBIs) in developing countries are not readily available or do not exist.

Aim

The aim of this study was to study the epidemiology of pediatric TBI in developing countries.

Methods

A retrospective study was conducted in a high-volume Neurosurgery Department where we reviewed pediatric cases presenting with TBI between January 2015 and December 2019. Data were collected from the electronic medical records including the patients’ demographics, neuro-vital signs, mechanism of TBI and treatment types. Radiological images were screened, and patients were classified according to the type of intracranial hemorrhage. The patient’s outcome and Glasgow Coma Scale on discharge were also recorded.

Result

Nine hundred and eighty-five cases with TBI were admitted over the period of 5 years. The average age was 53.3 months standard deviation (SD) of 39.4. Male gender accounted for 63.7% of the cases. The most common mechanisms of injuries were falls and road traffic accidents/motor vehicle collisions (63.3%, 18.3%), respectively. Nausea and vomiting followed by altered consciousness and drowsiness were the commonest presenting symptoms. Mild TBI accounted for 85.2% of the cases and the majority (92.08%) were treated conservatively (P < 0.005). 93.3% of the cases were categorized as mild head injury upon discharge. The mortality rate was 1.6% in severe TBI cases.

Conclusion

Children less than 4 years of age were highly affected by TBI. This study gives emergency physicians and neurosurgeons in developing countries an expectation about TBI in pediatric cases and the immediate management to prevent further complications.
Genome Resources of Verticillium dahliae VdGL16: The Causal Agent of Vascular Wilt on the Invasive Species Ailanthus altissima
Authors: Pisuttu Claudia , Sarrocco Sabrina , Cotrozzi Lorenzo , Baroncelli Riccardo , Lorenzini Giacomo
Published: December 2022

Verticillium species are known as plant pathogens responsible for wilt diseases in a large variety of dicotyledon plants and crops in many parts of the world. Here we present the draft genome sequence of Verticillium dahliae Kleb. (strain VdGL16) isolated in Italy from the invasive alien species Ailanthus altissima (Mill.; commonly known as tree-of-heaven) showing Verticillium wilt symptoms. The comparison between the newly sequenced genome with those publicly available revealed candidate genes putatively involved in pathogenicity. The genome represents a new useful source for future research on Verticillium genetics and biology as well as research on novel approaches in the control of A. altissima.
Mice harboring a R133L heterozygous mutation in LMNA exhibited ectopic lipid accumulation, aging, and mitochondrial dysfunction in adipose tissue
Authors: Qiu Ruojun , Wang Shuo , Lin Dingyi , He Yingzi , Huang Shaohan , Wu Beibei , Li Hong , Wang Min , Zheng Fenping
Published: December 2022

The LMNA gene encodes for the nuclear envelope proteins lamin A and C (lamin A/C). A novel R133L heterozygous mutation in the LMNA gene causes atypical progeria syndrome (APS). However, the underlying mechanism remains unclear. Here, we used transgenic mice (LmnaR133L/+ mice) that expressed a heterozygous LMNA R133L mutation and 3T3‐L1 cell lines with stable overexpression of LMNA R133L (by lentiviral transduction) as in vivo and in vitro models to investigate the mechanisms of LMNA R133L mutations that mediate the APS phenotype. We found that a heterozygous R133L mutation in LMNA induced most of the metabolic disturbances seen in patients with this mutation, including ectopic lipid accumulation, limited subcutaneous adipose tissue (SAT) expansion, and insulin resistance. Mitochondrial dysfunction and senescence promote ectopic lipid accumulation and insulin resistance. In addition, the FLAG‐mediated pull‐down capture followed by mass spectrometry assay showed that p160 Myb‐binding protein (P160 MBP; Mybbp1), the critical transcriptional repressor of PGC‐1α, was bound to lamin A/C. Increased Mybbp1 levels in tissues and greater Mybbp1‐lamin A/C binding in nuclear inhibit PGC‐1α activity and promotes mitochondrial dysfunction. Our findings confirm that the novel R133L heterozygous mutation in the LMNA gene caused APS are associated with marked mitochondrial respiratory chain impairment, which were induced by decreased PGC‐1α levels correlating with increased Mybbp1a levels in nuclear, and a senescence phenotype of the subcutaneous fat.
Liver‐specific deletion of microRNA‐34a alleviates ductular reaction and liver fibrosis during experimental cholestasis
Authors: Wan Ying , Zhou Tianhao , Slevin Elise , Koyama Sachiko , Li Xuedong , Harrison Kelly , Li Tian , Zhou Bingru , Lorenzo Sugeily Ramos , Zhang Yudian , Xu Wenjuan , Klaunig James E. , Wu Chaodong , Shetty Ashok K. , Huang Chiung‐Kuei , Meng Fanyin
Published: December 2022

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammatory responses and fibrotic scar formation leading to cholestasis. Ductular reaction and liver fibrosis are typical liver changes seen in human PSC and cholestasis patients. The current study aimed to clarify the role of liver‐specific microRNA‐34a in the cholestasis‐associated ductular reaction and liver fibrosis. We demonstrated that miR‐34a expression was significantly increased in human PSC livers along with the enhanced ductular reaction, cellular senescence, and liver fibrosis. A liver‐specific miR‐34a knockout mouse was established by crossing floxed miR‐34a mice with albumin‐promoter‐driven Cre mice. Bile duct ligation (BDL) induced liver injury characterized by necrosis, fibrosis, and immune cell infiltration. In contrast, liver‐specific miR‐34a knockout in BDL mice resulted in decreased biliary ductular pathology associated with the reduced cholangiocyte senescence and fibrotic responses. The miR‐34a‐mediated ductular reactions may be functioning through Sirt‐1‐mediated senescence and fibrosis. The hepatocyte‐derived conditioned medium promoted LPS‐induced fibrotic responses and senescence in cholangiocytes, and miR‐34a inhibitor suppressed these effects, further supporting the involvement of paracrine regulation. In conclusion, we demonstrated that liver‐specific miR‐34a plays an important role in ductular reaction and fibrotic responses in a BDL mouse model of cholestatic liver disease.
Innately expressed estrogen‐related receptors in the skeletal muscle are indispensable for exercise fitness
Authors: Sopariwala Danesh H. , Rios Andrea S. , Pei Guangsheng , Roy Anirban , Tomaz da Silva Meiricris , Thi Thu Nguyen Hao , Saley Addison , Van Drunen Rachel , Kralli Anastasia , Mahan Kristin , Zhao Zhongming , Kumar Ashok , Narkar Vihang A.
Published: December 2022

Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how exercise improves fitness. Here, we have elucidated the role of nuclear receptors, estrogen‐related receptor alpha and gamma (ERRα/γ) in regulating myofibrillar composition, contractility, and exercise capacity in skeletal muscle. We used muscle‐specific single or double (DKO) ERRα/γ knockout mice to investigate the effect of ERRα/γ deletion on muscle and exercise parameters. Individual knockout of ERRα/γ did not have a significant impact on the skeletal muscle. On the other hand, DKO mice exhibit pale muscles compared to wild‐type (WT) littermates. RNA‐seq analysis revealed a predominant decrease in expression of genes linked to mitochondrial and oxidative metabolism in DKO versus WT muscles. DKO muscles exhibit marked repression of oxidative enzymatic capacity, as well as mitochondrial number and size compared to WT muscles. Mitochondrial function is also impaired in single myofibers isolated from DKO versus WT muscles. In addition, mutant muscles exhibit reduced angiogenic gene expression and decreased capillarity. Consequently, DKO mice have a significantly reduced exercise capacity, further reflected in poor fatigue resistance of DKO mice in in vivo contraction assays. These results show that ERRα and ERRγ together are a critical link between muscle aerobic capacity and exercise tolerance. The ERRα/γ mutant mice could be valuable for understanding the long‐term impact of impaired mitochondria and vascular supply on the pathogenesis of muscle‐linked disorders.
Effect of intravenous antihypertensives on outcomes of severe hypertension in hospitalized patients without acute target organ damage
Authors: Ghazi Lama , Li Fan , Simonov Michael , Yamamoto Yu , Nugent James T. , Greenberg Jason H. , Bakhoum Christine Y. , Peixoto Aldo J. , Wilson F. Perry
Published: December 2022

Background:

Treatment of severe inpatient hypertension (HTN) that develops during hospitalization is not informed by guidelines. Intravenous (i.v.) antihypertensives are used to manage severe HTN even in the absence of acute target organ damage; however they may result in unpredictable blood pressure (BP) reduction and cardiovascular events. Our goal was to assess the association between i.v. antihypertensives and clinical outcomes in this population.

Methods:

This is a multihospital retrospective study of adults admitted for reasons other than HTN who develop severe HTN during hospitalization without acute target end organ damage. We defined severe HTN as BP elevation of systolic >180 or diastolic >110 mmHg. Treatment was defined as receiving i.v. antihypertensives within 3 h of BP elevation. We used overlap propensity score weighted Cox models to study the association between treatment and clinical outcomes during index hospitalization.

Results:

Of 224 265 unique, nonintensive care unit hospitalizations, 20 383 (9%) developed severe HTN, of which 5% received i.v. antihypertensives and 79% were untreated within 3 h of severe BP elevation. In the overlap propensity weighted population, patients who received i.v. antihypertensives were more likely to develop myocardial injury (5.9% in treated versus 3.6% in untreated; hazard ratio [HR]: 1.6 [1.13, 2.24]). Treatment was not associated with increased risk of stroke (HR: 0.7 [0.3, 1.62]), acute kidney injury (HR: 0.97 [0.81, 1.17]), or death (HR: 0.86 [0.49, 1.51]).

Conclusions:

Intravenous antihypertensives were associated with increased risk of myocardial injury in patients who develop severe HTN during hospitalization. These results suggest that i.v. antihypertensives should be used with caution in patients without acute target organ damage.
Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes
Authors: Agarwal Rajiv , Ruilope Luis M. , Ruiz-Hurtado Gema , Haller Hermann , Schmieder Roland E. , Anker Stefan D. , Filippatos Gerasimos , Pitt Bertram , Rossing Peter , Lambelet Marc , Nowack Christina , Kolkhof Peter , Joseph Amer , Bakris George L
Published: December 2022

Objective:

Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist with a short half-life. Its effects on cardiorenal outcomes were thought to be mediated primarily via nonhemodynamic pathways, but office blood pressure (BP) measurements were insufficient to fully assess hemodynamic effects. This analysis assessed the effects of finerenone on 24-h ambulatory BP in patients with chronic kidney disease and type 2 diabetes.

Methods:

ARTS-DN (NCT01874431) was a phase 2b trial that randomized 823 patients with type 2 diabetes and chronic kidney disease, with urine albumin-to-creatinine ratio ≥30 mg/g and estimated glomerular filtration rate of 30–90 ml/min per 1.73 m2 to placebo or finerenone (1.25–20 mg once daily in the morning) administered over 90 days. Ambulatory BP monitoring (ABPM) over 24 h was performed in a subset of 240 patients at screening, Day 60, and Day 90.

Results:

Placebo-adjusted change in 24-h ABPM systolic BP (SBP) at Day 90 was –8.3 mmHg (95% confidence interval [CI], –16.6 to 0.1) for finerenone 10 mg (n = 27), –11.2 mmHg (95% CI, –18.8 to –3.6) for finerenone 15 mg (n = 34), and –9.9 mmHg (95% CI, –17.7 to –2.0) for finerenone 20 mg (n = 31). Mean daytime and night-time SBP recordings were similarly reduced and finerenone did not increase the incidence of SBP dipping. Finerenone produced a persistent reduction in SBP over the entire 24-h interval.

Conclusions:

Finerenone reduced 24-h, daytime, and night-time SBP. Despite a short half-life, changes in BP were persistent over 24 h with once-daily dosing in the morning.
Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia
Authors: Cuomo Alessandro , Aguglia Eugenio , Biagini Stefano , Carano Alessandro , Clerici Massimo , D'Agostino Armando , De Filippis Sergio , De Giorgi Serafino , Goracci Arianna , Libri Claudia , Lombardi Francesco , Lupi Matteo , Maina Giuseppe , Martinotti Giovanni , Nigro Pietro , Pettorruso Mauro , Ricci Valerio , Rossi Eros , Russo Felicia , Fagiolini Andrea ,   The Italian Clinical Psychopharmacology Working Group
Published: December 2022

Purpose/Background

Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients.

Methods/Procedures

We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers.

Findings/Results

Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects.

Implications/Conclusions

The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.
Real-World Clinical Practice Among Patients With Bipolar Disorder and Chronic Kidney Disease on Long-term Lithium Therapy
Authors: Kumar Rakesh , Joseph Boney , Pazdernik Vanessa M. , Geske Jennifer , Nuñez Nicolas A. , Pahwa Mehak , Kashani Kianoush B. , Veldic Marin , Betcher Hannah K. , Moore Katherine M. , Croarkin Paul E. , Ozerdem Aysegul , Cuellar-Barboza Alfredo B. , McElroy Susan L. , Biernacka Joanna M. , Frye Mark A. , Singh Balwinder
Published: December 2022

Purpose

Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design.

Methods

Adult BD patients on LTLT for ≥1 year who enrolled in the Mayo Clinic Bipolar Disorder Biobank and developed CKD (stage 3) were included, and our study was approved by the Mayo Clinic Institutional Review Board. The primary outcome was the time to the first mood episode after CKD diagnosis among the lithium (Li) continuers and discontinuers. Cox proportional hazards models were used to estimate the time to the first mood episode. We tested for differences in other medication changes between the Li continuers and discontinuers group using Mantel-Haenszel χ2 tests (linear associations).

Results

Of 38 BD patients who developed CKD, 18 (47%) discontinued Li, and the remainder continued (n = 20). The median age of the cohort was 56 years (interquartile range [IQR], 48–67 years), 63.2% were female, and 97.4% were White. As compared with continuers, discontinuers had more psychotropic medication trials (6 [IQR, 4–6] vs 3 [IQR, 2–5], P = 0.02), a higher rate of 1 or more mood episodes (61% vs 10%, P = 0.002), and a higher risk of a mood episode after CKD diagnoses (Hazard Ratio, 8.38; 95% confidence interval, 1.85–38.0 [log-rank P = 0.001]].

Conclusions

Bipolar disorder patients on LTLT who discontinued Li had a higher risk for relapse and a shorter time to the first mood episode, suggesting a need for more thorough discussion before Li discontinuation after the CKD diagnosis.
α-Lipoic Acid as Adjunctive Treatment for Schizophrenia
Authors: De Lima David Nunes , Costa Filho Carlos Winston Luz , Frota Ilgner Justa , de Oliveira Alissandra Lima Barbosa , Menezes Carlos Eduardo de Souza , Chaves Filho Adriano José Maia , Viana Glautemberg de Almeida , Campos Eugênio de Moura , Collares Mônica , de Queiroz Maria Goretti Rodrigues , da Cruz Fonseca Said Gonçalvez , Vasconcelos Silvânia Maria Mendes , Macêdo Danielle S. , Sanders Lia Lira Olivier
Published: December 2022

Background/Purpose

There is evidence for low endogenous antioxidant levels and oxidative imbalance in patients with schizophrenia. A previous open-label study with α-lipoic acid (ALA), a potent antioxidant, improved patients' negative and cognitive symptoms and markers of lipid peroxidation. Here we report the results of a randomized double-blind, placebo-controlled study to verify the response of patients with schizophrenia to adjunctive treatment with ALA (100 mg/d) in a 4-month follow-up.

Methods

We conducted a 16-week, double-blind, placebo-controlled study of ALA at 100 mg/d dosages. We compared negative and positive symptoms, cognitive function, extrapyramidal symptoms, body mass index, and oxidative/inflammatory parameters between placebo and control groups.

Results

We found no significant improvement in body mass index, cognition, psychopathology, antipsychotic adverse effects, or oxidative stress and inflammation in the experimental group compared with placebo. The whole group of patients improved in several measures, indicating a strong placebo effect in this population. A surprising finding was a significant decrease in red blood cells, white blood cells, and platelets in the group treated with ALA.

Conclusions

The decrease in red blood cells, white blood cells, and platelet counts requires further investigation and attention when prescribing ALA for patients with schizophrenia.
Analysis on the drug rules and medical thought characteristics of Six Qi prescriptions in Yuansu Zhang’s Yixue Qiyuan: A Review
Authors: She Yanda , Su Ying , Wang Yan , Wang Renhe
Published: December 2022

Yixue Qiyuan is a representative work of Yuansu Zhang, a famous medical scientist during the Jin Dynasty. The contents of Five Yun and Six Qi are quite rich, especially the discussion on the treatment prescription and medication of Six Qi, which has a significant impact on the development of traditional Chinese medicine. Therefore, analyzing his drug rules and summarizing his medical thoughts can provide a reference for the clinical application of the theory of Five Yun and Six Qi. Based on the TCM inheritance auxiliary platform (V2.5), the data analyzed 63 first prescriptions and 134 drugs contained in the six Qi prescription sections of Yixue Qiyuan. Based on the frequency analysis, correlation rule analysis, four qi and five flavors, and meridian analysis, the formula rules for wind, summer heat, wet soil, fire, dryness, and cold water were obtained, and medical thought was summarized. Drug rules of prescription and medical thought can provide a useful reference for the classical study of traditional Chinese medicine and the application of the Six Qi theory in clinical practice.
Efficacy and safety of video laryngoscope in indwelling gastric tube in severe coma patients: A protocol for systematic review and meta-analysis
Authors: Gao Mengying , Wang Guoying , Zhang Yunjiao , Han Mei , Niu Huiping , Li Wenlin
Published: December 2022

Background:

We designed this systematic review and meta-analysis protocol to provide new medical evidence for clinical management by comparing the prognostic outcomes of visual laryngoscopy with those of conventional blinded insertion methods.

Methods:

We will intend to search English databases including Medicine, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, and Google Scholar. The Chinese databases, such as Wanfang, China Knowledge Network, and China Biomedical Literature Database will also be searched. The outcome measures include intubation success rate, pain score, intubation-related complications, patient satisfaction, operation time, and cost. The Jadad scale will be used to evaluate the methodological quality of each randomized controlled trial in this meta-analysis. We will use the Methodological Index of Non-Randomized Studies criteria to assess the risk of bias in non-randomized study. An I
2 value greater than 50% indicates the presence of significant heterogeneity. P < .05 in a 2-tailed test is considered statistically significant.

Results:

It is hypothesized that video laryngoscope will provide better outcomes compared with traditional blind gastric tube insertion.

Conclusions:

The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.
Interventional treatment of traumatic carotid-cavernous fistula: A case report
Authors: Wang Jiabin , Shen Xiaoming , Miao Niu , Yang Guofang , Zhang Mingqin , Yang Dongyi , Liu Yangyang , Wu Tao
Published: December 2022

Rationale:

Patients with traumatic carotid-cavernous fistula (TCCF) usually go to the ophthalmology department first because of the symptoms such as protrusion of eyes, edema and congestion of combined membrane, vision loss and so on. It is easy to be misdiagnosed and missed.

Patient concerns:

We report a case of left eye swelling and vision loss caused by TCCF after head injury due to traffic accident, which failed to respond to ophthalmic treatment for many times. The similar situation is very likely to cause panic among patients.

Diagnosis:

Cerebral angiography revealed left internal carotid-cavernous fistula (high flow type).

Interventions:

Left internal carotid artery covered stent implantation was performed.

Outcomes:

The fistulas and the original venous mass were completely covered by the covered stent, and the development of the vascular mass disappeared. The patient’s eye symptoms basically disappeared 14 days after the operation.

Lessons:

Interventional treatment of TCCF is effective.
Thematic analysis of articles on artificial intelligence with spine trauma, vertebral metastasis, and osteoporosis using chord diagrams: A systematic review and meta-analysis
Authors: Huang Yu-Po , Pao Jwo-Luen , Chien Tsair-Wei , Lin Jui-Chung John , Chou Po-Hsin
Published: December 2022

Background:

Spine trauma, vertebral metastases, and osteoporosis (SVO) can result in serious health problems. If the diagnosis of SVO is delayed, the prognosis may be deteriorated. The use of artificial intelligence (AI) is an essential method for minimizing the diagnostic errors associated with SVO. research achievements (RAs) of SVO on AI are required as a result of the greatest number of studies on AI solutions reported. The study aimed to: classify article themes using visualizations, illustrate the characteristics of SVO on AI recently, compare RAs of SVO on AI between entities (e.g., countries, institutes, departments, and authors), and determine whether the mean citations of keywords can be used to predict article citations.

Methods:

A total of 31 articles from SVO on AI (denoted by T31SVOAI) have been found in Web of Science since 2018. The dominant entities were analyzed using the CJAL score and the Y-index. Five visualizations were applied to report: the themes of T31SVOAI and their RAs in comparison for article entities and verification of the hypothesis that the mean citations of keywords can predict article citations, including: network diagrams, chord diagrams, dot plots, a Kano diagram, and radar plots.

Results:

There were five themes classified (osteoporosis, personalized medicine, fracture, deformity, and cervical spine) by a chord diagram. The dominant entities with the highest CJAL scores were the United States (22.05), the University of Pennsylvania (5.72), Radiology (6.12), and Nithin Kolanu (Australia) (9.88). The majority of articles were published in Bone, J. Bone Miner. Res., and Arch. Osteoporos., with an equal count (=3). There was a significant correlation between the number of article citations and the number of weighted keywords (F = 392.05; P < .0001).

Conclusion:

A breakthrough was achieved by displaying the characteristics of T31SVOAI using the CJAL score, the Y-index, and the chord diagram. Weighted keywords can be used to predict article citations. The five visualizations employed in this study may be used in future bibliographical studies.
Network pharmacology, molecular docking and bioinformatics reveal the mechanism of Tripterygii Wilfordii against Osteosarcoma
Authors: Zhang Yafang , Wei Junqiang , Kong Lingwei , Song Mingze , Zhang Yange , Xiao Xiangyu , Cao Haiying , Jin Yu
Published: December 2022

Osteosarcoma (OS) is a malignant bone tumor of mesenchymal origin. Tripterygii Wilfordii (TW) is a traditional Chinese medicine widely used for its anti-inflammatory and immunomodulatory effects. Various components of TW have been shown to have antitumor effects, however, no systematic study has been conducted to prove the anti-OS effects of TW. This study aimed to investigate the effects of TW on OS and its mechanism based on network pharmacology and molecular docking. The web pharmacology section includes the gathering of the active components of TW, the collection of predicted targets of TW and OS-related targets, the analysis of therapeutic targets of TW, the enrichment of gene ontology (GO), and the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). The Veen diagram showed 451 targets for OS treatment in TW. The therapeutic target enrichment analysis results showed that TW treated OS via multiple targets and pathways. TW can affect OS proliferation, apoptosis, migration, infiltration, and angiogenesis through a signaling network formed by hub genes that cascade through numerous signaling pathways. In addition, molecular docking results showed that triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin have relatively high potential to become drugs for patients with OS and improve the 5-year survival rate of patients with OS. Network pharmacology and molecular docking suggest that TW affects the biological behavior of OS through multiple pathways involving multiple targets, such as proliferation, apoptosis, migration, and infiltration. Upregulation of the cellular tumor antigen p53 (TP53) gene and downregulation of peroxisome proliferator-activated receptor gamma (PPARG) and signal transducer and activator of transcription 1-alpha/beta (STAT1) genes can prolong the survival time of patients with OS. Triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5 methyl-coumarin-3)-coumarin have a relatively high potential to become a treatment for patients with OS and improve 5-year survival of OS patients.
Exosomes: A new option for osteoporosis treatment
Authors: Huang Guijiang , Zhao Qianhao , Li Wenhu , Jiao Jianlin , Zhao Xin , Feng Dan , Tang Wei
Published: December 2022

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These cargo molecules are encapsulated in a lipid bilayer and internalized by target cells through receptor-ligand interactions or lipid membrane fusion. With the advancement of exosome research, exosome therapy for osteoporosis is fast becoming a research hotspot for researchers. This review aims to discuss the role of exosomes in the pathogenesis of osteoporosis. In addition, emerging diagnostic and therapeutic properties of exosomes are described to highlight the potential role of exosomes in osteoporosis.
Risk of birth defects in children conceived with assisted reproductive technology: A meta-analysis
Authors: Lu Yue , Liu Lele , Zhang Pingping , Sun Yanmei , Ma Cong , Li Yali
Published: December 2022

Background:

Although assisted reproductive technology (ART) is extensively used in couples with fertility problems, the risk of birth defects among infants conceived with ART is still a concern. Therefore, to more accurately assess the risk of birth defects after ART treatment, we performed a meta-analysis of all available cohort studies relating to birth defects among infants conceived with ART.

Methods:

We used an established strategy to search the databases of PUBMED, EMBASE, COCHRANE, WEB OF SCIENCE, CNKI, CBM and VIP for studies published between 2008 and 2020. Subgroup analyses and sensitivity analyses were used to examine sources of heterogeneity. Pooled adjusted odds ratios (ORs) were calculated using a fixed effects model. RevMan5.3 was used to draw a forest plot, and Stata14.0 was used to test for publication bias.

Results:

We included 14 cohort studies from different countries. The infants conceived with ART had a 1.22-fold higher likelihood of birth defects than children born after natural pregnancy(OR = 1.22, 95% CI [1.17, 1.28], P < .05). The prevalence of birth defects after ART treatment was higher in singleton births than in multiple births. In a meta-analysis of data from 6 studies, we found associations between ART and birth defects related to specifics organs: cardiovascular defects, OR = 1.51, 95% CI [1.34–1.69], P < .05; musculoskeletal defects, OR = 1.09, 95% CI [1.03–1.15], P < .05; urogenital defects, OR = 1.24, 95% CI [1.11–1.38], P < .05; central nervous system defects, OR = 1.33, 95% CI [1.14–1.55], P < .05; and orofacial defects, OR = 1.45, 95% CI [1.15–1.83], P < .05.

Conclusions:

ART treatment does present an increased risk of birth defects. The prevalence of birth defects after ART treatment is lower in multiple births than in singleton births. Further research is required to examine the risks for birth defects after ART treatment.
A pan-cancer analysis of the oncogenic role of polypyrimidine tract binding protein 1 (PTBP1) in human tumors
Authors: Huang Qing , Gu Shinong , Fang Jianqi , Li Xuanwen , Lin Lili
Published: December 2022

Background:

Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein that regulates several posttranscriptional events and is closely related to the development of multiple tumors. However, little is known about PTBP1. Thus, we carried out a systematic pan-cancer analysis to explore the relationship between PTBP1 and cancer.

Methods:

We used The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas datasets, as well as several bioinformatics tools, to explore the role of PTBP1 in 33 tumor types.

Results:

The expression of PTBP1 in most tumor tissues was higher than that in normal tissues. Survival analysis indicated that overexpression of PTBP1 generally predicted poor overall survival in patients with tumors such as adrenocortical carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, and skin cutaneous melanoma. In addition, we compared the phosphorylation and immune infiltration of PTBP1 in cancer-associated fibroblasts between normal and primary tumor tissues and explored the putative functional mechanism of tumorigenesis mediated by PTBP1.

Conclusion:

These results provide clues to better understand PTBP1 from the perspective of bioinformatics and highlight its importance in various human cancers.
Independent risk factor for surgical site infection after orthopedic surgery
Authors: Feng Yingfa , Feng Qi , Guo Peng , Wang Dong-lai
Published: December 2022

No significant progress has been made in the study of orthopedic surgical site infection (SSI) after different orthopedic surgery, and the analysis and prevention of risk factors for orthopedic SSI urgently need to be solved. A total of 154 patients underwent orthopedic surgery from April 2018 to December 2020. General information such as gender, age, marriage, diagnosis, surgical site, and anesthesia method was recorded. Statistical methods included Pearson chi-square test, univariate and multivariate logistic regression analyses, and receiver operating characteristic (ROC) curves. Based on Pearson’s chi-square test, sex (P = .005), age (P = .027), marriage (P = .000), diagnosis (P = .034), and surgical site (P = .000) were significantly associated with SSI after orthopedic surgery. However, in the multiple linear regression analysis, only the surgical site (P = .035) was significantly associated with SSI after orthopedic surgery. In terms of multivariate logistic regression level, surgical site (odds ratio [OR] = 1.568, P = .039) was significantly associated with SSI. ROC curves were constructed to determine the effect of the surgical site on SSI after different orthopedic surgery (area under the curve [AUC] = 0.577, 95% CI = 0.487–0.0.666). In summary, the surgical site is an independent risk factor for SSI after orthopedic surgery, and “trauma” is more likely to develop SSI than spine, arthrosis, and others.
Stent graft placement in anterior tibial artery pseudoaneurysm in a patient with type I neurofibromatosis: A case report
Authors: Woo Jonghun , Lee Jae Myeong , Shim Jongjoon
Published: December 2022

Rationale:

Vascular involvement manifests as aneurysms, stenosis, and arteriovenous malformations in patients with type I neurofibromatosis (NF-I). Aneurysms are rare; however, the renal artery is the most common site. Herein, we report a rare case of stent graft placement in an anterior tibial artery (ATA) pseudoaneurysm in a patient with NF-I.

Patient concerns:

A 52-year-old woman with NF-1 was admitted to the emergency room with painful swelling in the left lower leg. At presentation, the patient’s blood pressure was 100/60 mmHg and the hemoglobin level was 9 g/dL.

Diagnoses:

Computed tomography scan revealed a small aneurysm arising from the left ATA and an adjacent large hematoma.

Intervention:

Stent graft placement was performed to treat ATA pseudoaneurysm.

Outcomes:

After stent graft placement, the aneurysm disappeared and the distal flow was patent through the ATA.

Lessons:

Stent graft placement should be considered as another option for endovascular treatment in patients in whom coil embolization or surgery cannot be performed.
Differential effects of hyperhomocysteinemia on the lipid profiles and lipid ratios between patients with and without coronary artery disease: A retrospective observational study
Authors: Wu Dong-Feng , Liao Qin-Chen , Lu Feng , Wang Zhou , Yu Kun , Deng Jin-Long
Published: December 2022

This study aimed to investigate the differential effects of hyperhomocysteinemia (HHcy) on lipid profiles and lipid ratios between patients with coronary artery disease (CAD) and without CAD. The data of 872 CAD patients and 774 non-CAD controls were extracted from the information system of hospitalized patients. Serum homocysteine (Hcy), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, and ApoB concentrations were detected. HHcy was defined as a serum level of Hcy ≥ 15 μmol/L. The CAD patients had lower levels of HDL-C and ApoAI and higher levels of Hcy than the controls (P < .05). Serum TGs and HDL-C were negatively correlated with Hcy in controls. Serum HDL-C and ApoAI were negatively correlated with Hcy, and the ratios of TC/HDL-C, TG/HDL-C, LDL/HDL-C, and ApoB/ApoAI were positively correlated with Hcy in the CAD patients (P < .05). Although the trends for HHcy to decrease the lipid profiles were not different between the CAD and controls (P

interaction
 > 0.05), CAD with HHcy had lower HDL-C and ApoAI levels than those of subjects with normal Hcy; controls with HHcy had lower TC, LDL-C, and ApoB levels than those of subjects with normal Hcy (P < .05). There were different HHcy trends affecting the ratios of TC/HDL-C and LDL/HDL-C between the CAD patients and controls (P

interaction
for TC/HDL-C = 0.025; P

interaction
for LDL/HDL-C = 0.033). CAD patients with HHcy had a higher ratio of TC/HDL-C (P = .022) and LDL/HDL-C (P = .045) than those of patients with normal Hcy, but in the controls, the subjects with HHcy exhibited a trend toward a decreased ratio of TC/HDL-C (P = .481) and LDL/HDL-C (P = .303). There were differential effects of HHcy on the lipid ratios between CAD and non-CAD patients. HHcy was related to higher ratios of TC/HDL-C and LDL/HDL-C in patients with CAD.