bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Traumatic Ankle Arthrotomies: Computed Tomography Scan vs. Saline Load Test
Authors: Kallevang LT Jonathan K. , Berault LT Thomas J. , Olsen LCDR Aaron A. , Zuppke Julia N. , Clark LCDR James K. , Douglas CDR Thomas J. , Smith CDR Christopher S.
Published: January 2024

OBJECTIVE:

Periarticular wounds present a common diagnostic dilemma for emergency providers and orthopedic surgeons, as traumatic arthrotomies (TA) often necessitate different management from superficial soft tissue wounds. Historically, TA have been diagnosed with the saline load test (SLT). Computed tomography (CT) scan has been studied as an alternative to SLT in diagnosing TA in several joints, but there is limited data specifically pertaining to the ankle. This study aimed to compare the ability of a CT scan to identify an ankle TA versus a traditional SLT. The hypothesis was there would be no significant difference between a CT scan and SLT in diagnosing ankle TA in a cadaveric model.

METHODS:

This cadaveric study utilized ten thawed fresh-frozen cadaveric ankles. A baseline CT scan was performed to ensure no intra-articular air existed before simulated TA. After the baseline CT, a 1 cm TA was created in the anterolateral arthroscopy portal site location. The ankles then underwent a post-arthrotomy CT scan to evaluate for the presence of intra-articular air. After the CT scan, a 30 mL SLT was performed using the anteromedial portal site location.

RESULTS:

Following arthrotomy, intra-articular air was visualized in seven of ten cadavers in the post-arthrotomy CT scan. All the ankles had fluid extravasation during the SLT with less than 10 mL of saline. The sensitivity of the SLT for TA was 100% versus 70% for the CT scan.

CONCLUSION:

The SLT was more sensitive in diagnosing 1 cm ankle TA than a CT scan in a cadaveric model.
Medicaid Expansion and Racial–Ethnic and Sex Disparities in Cardiovascular Diseases Over 6 Years: A Generalized Synthetic Control Approach
Authors: Nianogo Roch A. , Zhao Fan , Li Stephen , Nishi Akihiro , Basu Sanjay
Published: January 2024

Background:

Studies have suggested Medicaid expansion enacted in 2014 has resulted in a reduction in overall cardiovascular disease (CVD) mortality in the United States. However, it is unknown whether Medicaid expansion has a similar effect across race–ethnicity and sex. We investigated the effect of Medicaid expansion on CVD mortality across race–ethnicity and sex.

Methods:

Data come from the behavioral risk factor surveillance system and the US Centers for Disease Control’s Wide-ranging Online Data for Epidemiologic Research, spanning the period 2000–2019. We used the generalized synthetic control method, a quasi-experimental approach, to estimate effects.

Results:

Medicaid expansion was associated with −5.36 (mean difference [MD], 95% confidence interval [CI] = −22.63, 11.91) CVD deaths per 100,000 persons per year among Blacks; −4.28 (MD, 95% CI = −30.08, 21.52) among Hispanics; −3.18 (MD, 95% CI = −8.30, 1.94) among Whites; −5.96 (MD, 95% CI = −15.42, 3.50) among men; and −3.34 (MD, 95% CI = −8.05, 1.37) among women. The difference in mean difference (DMD) between the effect of Medicaid expansion in Blacks compared with Whites was −2.18; (DMD, 95% CI = −20.20, 15.83); between that in Hispanics compared with Whites: −1.10; (DMD, 95% CI = −27.40, 25.20) and between that in women compared with men: 2.62; (DMD, 95% CI = −7.95, 13.19).

Conclusions:

Medicaid expansion was associated with a reduction in CVD mortality overall and in White, Black, Hispanic, male, and female subpopulations. Also, our study did not find any difference or disparity in the effect of Medicaid on CVD across race–ethnicity and sex–gender subpopulations, likely owing to imprecise estimates.
Acupuncture for ischemic stroke: Where are we now?
Authors: Zhu Weiming , Jia Qingqing , Ferreira Alberto Cantidio , Jiang Hailun , Zhang Jieying , Li Boxuan , Zhang Menglong , Zhuo Bifang , Lyu Yuanhao , Chen Junjie , Li Li , Tian Guang , Deng Shizhe , Meng Zhihong , Shi Xuemin
Published: January 2024

Acupuncture is an effective treatment for ischemic stroke (IS) and plays a key role in neurological rehabilitation after IS. Acupuncture can improve the clinical symptoms of various complications after IS, including motor dysfunction, swallowing disorders, speech disorders, cognitive impairment, depression, insomnia, and fatigue. However, the mechanisms underlying the effects of acupuncture in IS remain unclear. Available evidence suggests that acupuncture may exert neuroprotective effects through neuroplasticity (neurogenesis and synaptogenesis), angiogenesis, cell proliferation and apoptosis, and regulation of oxidative stress, inflammation, and immunity. Further studies should be conducted to improve the high-quality evidence-based system of acupuncture intervention for IS, by focusing on the clinical and basic research design, increasing the sample size, standardizing and quantifying the standards of acupuncture operations, using multidisciplinary techniques and methods to systematically explore the key targets of acupuncture intervention for IS, and reveal the efficacy and mechanism of acupuncture in the treatment of IS.
Comparison of refractive surgeries (SMILE, LASIK, and PRK) with and without corneal crosslinking: systematic review and meta-analysis
Authors: Hira Sara , Klein Heffel Kélen , Mehmood Fatima , Sehgal Kush , Felix De Farias Santos Ana Clara , Steuernagel Del Valle Giulia
Published: January 2024

Corneal crosslinking (CXL) is used for treating keratoconus and post–laser in situ keratomileusis ectasia. However, refractive surgery is not usually performed with prophylactic CXL. Therefore, we performed a meta-analysis comparing outcomes of refractive surgeries with vs without prophylactic CXL. We systematically searched databases for studies comparing refractive surgeries for myopic correction with vs without prophylactic corneal crosslinking. Review Manager 5.4.1 was used to perform statistical analysis. We included 2820 eyes from 28 studies. Compared with refractive surgery alone, surgery with prophylactic CXL resulted in decreased central corneal thickness, corrected distance visual acuity logMAR, and safety and efficacy indices. There were no significant differences in postoperative uncorrected distance visual acuity of 20/20 or better at ≥12 months and other visual outcomes among both groups. More randomized controlled trials with standard crosslinking protocols are needed to analyze the prophylactic use of crosslinking with refractive surgeries.
Nephrologist follow-up care for the acute kidney injury-chronic kidney disease continuum and clinical outcomes: A systematic review and meta-analysis
Authors: Hsieh Chih-Chieh , Chen Sheng-Yin , Chen Jui-Yi , Pan Heng-Chih , Liao Hung-Wei , Wu Vin-Cent
Published: January 2024

Background:

Acute kidney injury (AKI) to chronic kidney disease (CKD) continuum will increase patients’ risk of mortality and long-term dialysis. The aim of the present meta-analysis is to explore the effectiveness of nephrologist care and focus on the follow-up in patients with AKI.

Methods:

A systematic search of studies on nephrologist care for the AKI to CKD continuum has been conducted from PubMed and other different databases. Briefly, the primary outcome is the odds ratio of mortality as well as the secondary outcome is de novo renal replacement therapy.

Results:

This research includes one randomized controlled trial (RCT) and four cohort studies comprised of 15 541 participants in total. The quantitative analysis displays a lower mortality rate with nephrologist care versus non-nephrologist care in patients’ discharge after a hospitalization complicated by AKI (odds ratio: 0.768; 95% CI, 0.616-0.956). By means of Trial Sequential Analysis (TSA), we conclude that nephrologist care after an AKI episode declines 30% relative risks of all-cause mortality.

Conclusion:

Nephrologist care for AKI patients after a hospitalization significantly has reduced mortality compared to those followed up by non-nephrologists. There is a trend toward a potentially superior survival rate with nephrologist care has been going well in the recent years.
Characteristics of bone metabolism in the male patients with diabetic neuropathy
Authors: Huang Dong-Ni , Zeng Yue , Ding Hui-Ru , Zhang Zi-Kai , Wang Yu , Han Dong-Xu , Zhang Xiu-Zhen , Song Li-Ge
Published: January 2024

Background:

This study aimed to evaluate the characteristics of bone metabolism and fracture risk in the type 2 diabetes mellitus (T2DM) patients with distal symmetric polyneuropathy (DSPN).

Methods:

A total of 198 T2DM individuals were recruited from January 2017 to December 2020. Patients with DSPN were evaluated by strict clinical and sensory thresholds. Biochemical parameters and bone mineral density (BMD) were measured. The BMD, bone turnover markers, and probability of fracture were compared between two groups, and the factors related to BMD and probability of hip fracture in 10 years were further explored.

Results:

Compared with type 2 diabetes mellitus without distal symmetric polyneuropathy (T2DN−) patients, type 2 diabetes mellitus with distal symmetric polyneuropathy (T2DN+) patients had lower level of cross-linked C-telopeptide (CTX) (0.32 ± 0.19 vs 0.38 ± 0.21 ng/mL, p = 0.038) and higher level of bone-specific alkaline phosphatase (BALP) (15.28 ± 5.56 vs 12.58 ± 4.41 μg/mL, p = 0.003). T2DN+ patients had higher BMD of lumbar L1-L4 (1.05 ± 0.19 vs 0.95 ± 0.37, p = 0.027) and higher probability of hip fracture (0.98 ± 0.88 vs 0.68 ± 0.63, p = 0.009) as compared to T2DN− individuals. Univariate correlation analysis showed that BALP level (coefficient (coef) = −0.054, p = 0.038), CTX level (coef = −2.28, p = 0.001), and hip fracture risk (coef = −1.02, p < 0.001) were negatively related to the BMD of L1-L4. As for the risk of hip fracture evaluated by WHO Fracture Risk Assessment Tool (FRAX), age (coef = 0.035, p < 0.001), use of insulin (coef = 0.31, p =0.015), and levels of BALP (coef = 0.031, p = 0.017) and CTX (coef = 0.7, p = 0.047) were positively related to the risk of hip fracture. Multivariate regression analysis showed that CTX level (coef = −1.41, p = 0.043) was still negatively related to BMD at the lumbar spine.

Conclusion:

This study indicates that T2DM patients with DSPN have special bone metabolism represented by higher BALP level and lower CTX level which may increase BMD at the lumbar spine.
Reliability of a Musculoskeletal Imaging Competency Examination for Physical Therapists
Authors: Burley Troy , Cahanin Richard L. , Brody Lori T. , Boissonnault William G. , Ross Michael D.
Published: January 2024

Introduction.

The Burley Readiness Examination (BRE) for Musculoskeletal (MSK) Imaging Competency assesses physical therapists' baseline MSK imaging competency. Establishing its reliability is essential to its value in determining MSK imaging competency. The purpose of this study was to test the reliability of the BRE for MSK Imaging Competency among physical therapists (PTs) with varying levels of training and education.

Review of Literature.

Previous literature supports PTs' utility concerning diagnostic imaging; however, no studies directly measure their competency. With PTs expanding their practice scope and professional PT education programs, increasing their MSK imaging instruction, assessing competency becomes strategic in determining the future of MSK education and training.

Subjects.

One hundred twenty-three United States licensed PTs completed the BRE.

Methods.

Physical therapists completed the BRE through an online survey platform. Point biserial correlation (rpb) was calculated for each examination question. Final analyses were based on 140 examination questions. Examination scores were compared using independent sample t-test and one-way analysis of variance. Chi-square tests and odds ratios (ORs) assessed the relationship of a passing examination score (≥75%) and the type of training. Reliability of the BRE was assessed using Cronbach's alpha (α).

Results.

Mean overall examination score was 75.89 ± 8.56%. Seventy PTs (56.9%) obtained a passing score. Physical therapists with additional MSK imaging training, board certification, and residency or fellowship training scored significantly higher (P < .001) compared with those with only entry-level PT program education. Physical therapists with additional MSK imaging training scored significantly higher (x̄ = 81.07% ± 8.93%) and were almost 5 times (OR = 4.74, 95% CI [1.95–11.50]) as likely to achieve a passing score than those without. The BRE demonstrated strong internal consistency (Cronbach's α = 0.874).

Discussion and Conclusions.

The BRE was reliable, consistently identifying higher examination scores among those with increased MSK imaging training. Training in MSK imaging influenced competency more than other factors. The BRE may be of analytical value to PT professional and postprofessional programs.
A Rare Presentation of Pica Disorder in Soap Ingestion Variant
Authors: Sousa Rui , Cunha Francisco , Abreu Joana , Cunha Nuno
Published: January 2024

Pica indicates the persistent ingestion of inedible substances over a period of at least 1 month, being discordant to the individual's cognitive development level and not directly attributable to cultural or social normative practices. The literature suggests that the prevalence of pica varies significantly according to the social and clinical context. It can co-occur with psychiatric disorders, with its etiology being poorly understood and most likely multifactorial. In this article, we report the case of a patient in her 50s with a clinical setting compatible with soap ingestion variant of pica disorder. In addition to the variety of ingested substances, pica can be associated with heterogeneous behavior, mainly of the obsessive-compulsive spectrum. Despite recent research, this condition is still a target of much speculation. This is a very rare and challenging presentation of a soap ingestion variant of pica with very few similar cases described to date.
Correlates of Menarcheal Age in a Psychiatric Sample of Adolescents
Authors: Stumper Allison , Thomas Sarah A. , Zaidi Zaharah A. , Fydenkevez Megan A. , Maron Micaela , Wolff Jennifer C. , Peters Jessica R.
Published: January 2024

Early pubertal timing is associated with more adverse childhood experiences (ACEs) and increased risk for psychopathology during adolescence. However, most work to date has used community or epidemiological samples, and it remains unclear whether these associations persist in acute clinical samples. The present study examined associations between age at menarche and ACEs, psychiatric symptoms, and emotion regulation difficulties in a sample of N = 140 adolescents on a psychiatric inpatient unit. Youth with early menarche reported higher levels of depressive symptoms, more severe suicidal ideation, and greater difficulty with emotion regulation than youth with normative age at menarche. There was a marginal effect of youth with early menarche reporting more ACEs and more anxiety symptoms. These results suggest menarcheal age, and ACEs may be useful risk factors to assess in inpatient settings to predict risk for more severe outcomes, and future research on pubertal timing in high acuity settings is warranted.
Differences in STI/HIV Burden and Sexual Health Care–Seeking Behavior Among First- and Second-Generation Migrant and Western-Born Male Sex Workers Who Have Sex With Men in the Netherlands: A Retrospective Cohort Study
Authors: Peters Charlotte M.M. , Evers Ymke J. , Kampman Carolina J.G. , Theunissen-Lamers Marie-José , Van Den Elshout Mark A.M. , Dukers-Muijrers Nicole H.T.M. , Hoebe Christian J.P.A.
Published: January 2024

Background

Globally, migrant sex workers have a higher burden of sexually transmitted infections (STI)/human immunodeficiency virus (HIV). This large study aimed to assess demographics, STI/HIV burden, and sexual health care–seeking behavior of first-generation migrant and second-generation migrant male sex workers who have sex with men (MSW-MSM) versus Western-born MSW-MSM.

Methods

Coded STI clinic consultations (n = 6970) from 3116 individual MSW-MSM attending any Dutch STI clinic between 2016 and 2021 were included. First-generation migrant: born outside of northern/central/southern/western Europe/North America/Oceania. Second-generation migrant: ≥1parent born outside of northern/central/southern/western Europe/North America/Oceania. Multivariable logistic regression analysis assessed associations between MSW-MSM groups and STI in first consultation in the data. A Cox proportional hazard regression compared the incidence of a first repeat consultation between migration groups, stratified by STI in first consultation. All analyses were adjusted for age and urbanity of STI clinic region.

Results

First-generation migrant MSW-MSM (n = 1085) were mostly born in Latin America (50%), whereas second-generation migrant MSW-MSM (n = 368) mostly originated from North Africa (30.4%). The proportion of STI diagnoses differed (33.2%, 29.3%, 23.3%; P < 0.001) between the first-generation migrant, second-generation migrant, and Western-born MSW-MSM. First-generation migrant MSW-MSM versus Western-born had an adjusted odds ratio of 1.6 (95% confidence interval, 1.3–1.9) of STI diagnosis in the first consultation. First-generation migrant MSW-MSM versus Western-born had an adjusted hazard ratio of 1.5 (95% confidence interval, 1.3–1.8) of having a first repeat consultation at any time, when stratified for no STI in the first consultation.

Conclusions

The STI/HIV burden is high among all 3 MSW-MSM groups. First-generation migrants have higher odds of STI, but retention in care seems similar. Results highlight the importance of low-threshold STI testing and care for (migrant) MSW-MSM.
EBV-positive Nodal T-Cell and NK-Cell Lymphoma
Authors: Yu Fang , Wang Jinghan , Ke Zhonghe , Zhang Yafei , Xu Liming , Zhang Han , Huang Ke , Cheng Fei , Yang Hanjin , Wang Lijun , Wang Zhaoming , Shou Lihong , Yu Wenjuan , Fang Hong , Medeiros L. Jeffrey , Wang Wei
Published: January 2024

Epstein-Barr virus (EBV)-positive nodal T-cell and NK-cell lymphoma is a rare neoplasm of cytotoxic T-cell or NK-cell lineage. Here, we report 26 cases affecting 14 men and 12 women with a median age of 52 years. All patients presented with disease involving multiple lymph nodes, and 20 of 22 (91%) fully staged patients had advanced Ann Arbor stage disease. Spleen, liver, and bone marrow were involved in 70%, 50%, and 52% of cases, respectively. These patients had a dismal prognosis with a median survival of 30 days. Histologically, lymph nodes were replaced by lymphoma in a diffuse pattern. Lymphoma cells were variable in size and large cell morphology was seen in 62% of cases. The neoplastic cells were CD4-/CD8- in 14 (54%) cases and CD4-/CD8+ in 12 (46%) cases. CD56 was positive in 14 (54%) cases. CD30 was positive in 20 (77%) cases; a strong and diffuse pattern was observed in 14 (54%) cases, mimicking, in part, anaplastic large cell lymphoma (ALCL). CD30 expression was associated with younger age and large cell morphology. In summary, EBV+ nodal T-cell and NK-cell lymphoma is an aggressive disease with a poor prognosis. These neoplasms are heterogeneous at the morphologic and immunophenotypic levels. Diffuse and strong expression of CD30 could potentially lead to a misdiagnosis of ALCL if EBV evaluation is not performed. Distinguishing between EBV+ nodal T-cell and NK-cell lymphoma from ALCL is important because treatment strategy and prognosis differ. CD30 expression offers a potential therapeutic target for patients with this aggressive disease.
Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study
Authors: Badary Dalia M. , Elsaied Huda , Abdel-Fadeil Mahmoud R. , Ali Mohammed K. , Abou-Taleb Hisham , Iraqy Heba M.
Published: January 2024

Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.
Subjective Long-Term Outcomes After Vaginal Native Tissue Hysteropexy: Cohort Study
Authors: Lange Sören , Carlin Greta , Zängle Roxana , Heinzl Florian , Umek Wolfgang , Bodner-Adler Barbara
Published: January 2024

Importance

There are still doubts about long-term satisfaction rates of native tissue uterine preserving surgical techniques for pelvic organ prolapse.

Objective

The objective of this study was to compare long-term subjective success rates and satisfaction rates between vaginal sacrospinous hysteropexy (SSHP) and vaginal hysterectomy with uterosacral ligament suspension (VH-USLS).

Study Design

This was a retrospective single-center, observational matched cohort study in women receiving either SSHP or VH-USLS between 2004 and 2021. Primary outcome was overall subjective success (combined outcome of absence of bulge nor retreatment, and satisfaction with operation) at least 12 months after surgery. Satisfaction with the operation was defined as a combined Patient Global Impression of Improvement rating ≤ 2 and a patient satisfaction score ≥7.

Results

Of 583 patients, 192 patients could be matched (SSHP, 96; VH-USLS, 96), with 55% (SSHP, 60; VH-USLS, 45) participating at the telephone interview. Mean follow-up time was 77 months for VH-USLS, and 36 months for SSHP, respectively. No difference in overall subjective success rates was found between the groups (45% VH-USLS and 51% SSHP; P = 0.54). Overall satisfaction was similar between both groups (70% vs 71%, P = 0.90). Logistic regression found no influence of duration of follow-up and the overall subjective success rate. Both procedures would be recommended to a relative or friend by a large majority of patients (88% vs 85%, P = 0.761). Operative time and hospitalization time were significantly shorter in the SSHP group. No serious complications were reported.

Conclusions

Overall success rates did not differ between both procedures after at least 1 year of follow-up with relatively high satisfaction rates. Sacrospinous hysteropexy had shorter operative time and shorter duration of hospitalization.
Comparative analysis of virulence gene profiles of Escherichia coli from clinical and non-clinical sources in Rivers State, Nigeria

Authors: Abeni Barira Azeez , Frank-Peterside Nnenna , Otokunefor Kome
Published: January 2024

Traditionally, the presence of virulence features have been thought to be a key factor in differentiating pathogenic from commensal strains. An understanding of virulence potential of Escherichia coli isolates from various sources is essential to help shed light on potential contamination/transmission rates between the various sources. This study was therefore aimed at exploring the occurrence of specific virulence genes and gene profiles associated with Escherichia coli from clinical and non-clinical sources in Rivers State, Nigeria.
Two hundred samples from clinical (urine and feces) and non-clinical (soil and poultry droppings) sources (50 each) were analyzed using standard microbiological procedures. DNA was extracted from isolates presumptively identified as Escherichia coli using PrestoTM Mini gDNA Bacteria-Kit Quick protocol following the manufacturer’s instructions. Isolate identities were confirmed using E. coli specific 16S rRNA primers and confirmed isolates screened for the presence of six virulence genes (Afimbriae binding adhesin (afa), type 1 fimbriae (fimH), P-fimbrial Usher Protein (papC)), iron acquisition systems: aerobactin (aer), Cytotoxic necrotizing factor I (cnf1) and alpha hemolysin (hly).
Results showed that all isolates haboured at least one of the tested virulence genes, with fimH (97%) as the most prevalent virulence gene and papC the least commonly occurring (35%). A higher occurrence of virulence genes was noted in non-clinical isolates though Hly and cnf were not detected at all in any of the isolates studied (0%). Ten different profiles were observed with the afaCc-aer-fimH profile the most commonly occurring virulence gene profile in general (33.3%). For non-clinical isolates however, the aer-afaCc-fimH-papC was the most commonly occurring profile (42.9%).
This study shows that the test clinical and non-clinical Escherichia coli do not carry distinct virulence gene profiles. Hence the virulence genes tested for in this study cannot be used to tell whether an isolate is of a clinical source or not.
Corynebacterium mendelii sp. nov., a novel bacterium isolated from Adélie penguin oral cavity
Authors: Koublová Vendula , Sedlář Karel , Sedláček Ivo , Musilová Jana , Staňková Eva , Králová Stanislava , Koudelková Sylva , Krsek Daniel , Švec Pavel
Published: January 2024

The taxonomic status of strain P5891T, isolated from an Adélie penguin beak swab, was investigated. Based on the 16S rRNA gene sequence, the strain was identified as a potentially novel

Corynebacterium

species, with the highest sequence similarities to

Corynebacterium rouxii

FRC0190T (96.7 %) and

Corynebacterium epidermidicanis

DSM 45586T (96.6 %). The average nucleotide identity values between strain P5891T and

C. rouxii

FRC0190T and

C. epidermidicanis

DSM 45586T were 68.2 and 69.2 %, respectively. The digital DNA–DNA hybridization values between strain P5891T and

C. rouxii

FRC0190T and

C. epidermidicanis

DSM 45586T were 23.7 and 21.4 %, respectively. Phylogenetic trees based on the 16S rRNA sequence placed strain P5891T in a separate branch with

Corynebacterium canis

1170T and

Corynebacterium freiburgense

1045T, while a phylogenomic tree based on the

Corynebacterium

species core genome placed the strain next to

Corynebacterium choanae

200CHT. Extensive phenotyping and genomic analyses clearly confirmed that strain P5891T represents a novel species of the genus

Corynebacterium

, for which the name Corynebacterium mendelii sp. nov. is proposed, with the type strain P5891T (=CCM 8862T=LMG 31627T).
Transmission dynamics and pathogenesis differ between pheasants and partridges infected with clade 2.3.4.4b H5N8 and H5N1 high-pathogenicity avian influenza viruses
Authors: Seekings Amanda H. , Liang Yuan , Warren Caroline J. , Hjulsager Charlotte K. , Thomas Saumya S. , Lean Fabian Z. X. , Nunez Alejandro , Skinner Paul , Selden David , Falchieri Marco , Simmons Hugh , Brown Ian H. , Larsen Lars E. , Banyard Ashley C. , Slomka Marek J.
Published: January 2024

During the UK 2020–2021 epizootic of H5Nx clade 2.3.4.4b high-pathogenicity avian influenza viruses (HPAIVs), high mortality occurred during incursions in commercially farmed common pheasants (Phasianus colchicus). Two pheasant farms, affected separately by H5N8 and H5N1 subtypes, included adjacently housed red-legged partridges (Alectoris rufa), which appeared to be unaffected. Despite extensive ongoing epizootics, H5Nx HPAIV partridge outbreaks were not reported during 2020–2021 and 2021–2022 in the UK, so it is postulated that partridges are more resistant to HPAIV infection than other gamebirds. To assess this, pathogenesis and both intra- and inter-species transmission of UK pheasant-origin H5N8-2021 and H5N1-2021 HPAIVs were investigated. Onward transmission to chickens was also assessed to better understand the risk of spread from gamebirds to other commercial poultry sectors. A lower infectious dose was required to infect pheasants with H5N8-2021 compared to H5N1-2021. However, HPAIV systemic dissemination to multiple organs within pheasants was more rapid following infection with H5N1-2021 than H5N8-2021, with the former attaining generally higher viral RNA levels in tissues. Intraspecies transmission to contact pheasants was successful for both viruses and associated with viral environmental contamination, while interspecies transmission to a first chicken-contact group was also efficient. However, further onward transmission to additional chicken contacts was only achieved with H5N1-2021. Intra-partridge transmission was only successful when high-dose H5N1-2021 was administered, while partridges inoculated with H5N8-2021 failed to shed and transmit, although extensive tissue tropism was observed for both viruses. Mortalities among infected partridges featured a longer incubation period compared to that in pheasants, for both viruses. Therefore, the susceptibility of different gamebird species and pathogenicity outcomes to the ongoing H5Nx clade 2.3.4.4b HPAIVs varies, but pheasants represent a greater likelihood of H5Nx HPAIV introduction into galliforme poultry settings. Consequently, viral maintenance within gamebird populations and risks to poultry species warrant enhanced investigation.
Comparative transcriptome database forCamellia sinensisreveals genes important for flavonoid synthesis in tea plants
Authors: Zheng Xinghai , Mohd Ali Zahin , Lim Peng Ken , Mutwil Marek , Wang Yuefei
Published: January 2024

Tea, as one of the most popular beverages in the world, possesses a plethora of secondary metabolites that are beneficial to human health. Tea plants (Camellia sinensis) exhibit rich genetic diversity, where different cultivars can vary significantly in terms of yield, adaptability, morphology, and composition of secondary metabolites. Many tea cultivars have been the subject of much research interest, which have led to the accumulation of publicly available RNA-seq data. As such, it has become possible to systematically summarize the characteristics of different cultivars at the transcriptomic level, identify valuable functional genes, and infer gene functions through co-expression analysis. Here, the transcriptomes of 9 cultivars ofCamellia sinensiswere assembled and combined with the coding sequences of 13 cultivars ofCamellia sinensisto study the differences and similarities of gene expression and biological functions among cultivars. To give access to this data, we present TeaNekT (https://teanekt.sbs.ntu.edu.sg/), a web resource that provides user-friendly tools and interactive visualizations that facilitates the prediction of gene functions of various tea cultivars. We used TeaNekT to perform cross-cultivar comparison of co-expressed gene neighborhoods, clusters, and tissue-specific gene expression. We show that the members of the chalcone synthase (CHS) gene family, important for flavonoid synthesis, exhibit the highest expression variability, specific expression in leaves and buds, and significant modulation by methyl jasmonate (MeJA) treatment. By using comparative co-expression tools of TeaNekT, we identified multiple conserved genes involved in flavonoid biosynthesis among cultivars that have not been previously studied, warranting further research.
DCs targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors
Authors: López-Rodríguez Lucía , Morosi Luciano , La Terza Federica , Bourdely Pierre , Rospo Giuseppe , Amadio Roberto , Piperno Giulia Maria , Russo Valentina , Volponi Camilla , Vodret Simone , Joshi Sonal , Giannese Francesca , Lazarevi Dejan , Germano Giovanni , Stoitzner Patrizia , Bardelli Alberto , Dalod Marc , Pace Luigia , Caronni Nicoletta , Guermonprez Pierre , Benvenuti Federica
Published: January 2024

Cross-presentation by type 1 cDCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels ofbona-fideneoantigens (neoAgs) remains unclear. Here we generated a non-small cell lung cancer model with distinct ranges of TMB and MHC-I neoepitopes to test immunogenicity and response to Flt3L+αCD40 (DC-therapy). We found that cDC1 are required to broaden the pattern of CD8 responses to basal and acquired neoAgs and DC-therapy strongly inhibits the growth of TMBhightumors. In contrast, TMBlowtumors induce weaker responses that are not sufficient to block progression. scRNA transcriptional analysis, immune profiling and functional assays show that DC-therapy triggers the accumulation of lung cDC1 with increased immunostimulatory properties and CD8 T cells with enhanced cytotoxic functions and reduced exhaustion, most prominently in neoAgshightumors. We conclude that boosting cDC1 activity is critical to broaden the diversity of anti-tumoral CD8 T cell responses and to leverage neoAgs content for therapeutic advantage.
Non-physiologic interaction of MG53 with insulin receptor and lack of evidence for MG53’s role in controlling insulin-stimulated Akt phosphorylation in muscle, heart and liver tissues
Authors: Lee Kyung Eun , Nishi Miyuki , Kim Jongsoo , Murayama Takashi , Dawson Zachary , Wang Xiaoliang , Zhou Xinyu , Tan Tao , Cai Chuanxi , Takeshima Hiroshi , Park Ki Ho
Published: January 2024

Rationale

MG53’s known function in facilitating tissue repair and anti-inflammation has broad applications to regenerative medicine. There is controversy regarding MG53’s role in the development of type 2 diabetes mellitus (T2DM).

Objective

This study aims to address this controversy – whether MG53’s myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues.

Study Design

We determined the binding affinity of the recombinant human MG53 (rhMG53) to the insulin receptor extracellular domain (IR-ECD) and found low affinity of interaction with Kd(>480 nM). Using cultured C2C12 myotubes and HepG2 cells, we found no effect of rhMG53 on insulin-stimulated Akt phosphorylation (p-Akt). We performed in vivo assay with C57BL/6J mice subjected to insulin stimulation (1 U/kg, intraperitoneal injection) and observed no effect of rhMG53 on insulin-stimulated p-Akt in muscle, heart and liver tissues.

Conclusion

Overall, our data suggest that rhMG53 can bind to the IR-ECD, however has a low likelihood of a physiologic role, as the Kdfor binding is ∼10,000 higher than the physiologic level of MG53 present in the serum of rodents and humans (∼10 pM). Our findings question the notion proposed by Xiao and colleagues – whether targeting circulating MG53 opens a new therapeutic avenue for T2DM and its complications.
Identifying genomic data use with the Data Citation Explorer
Authors: Byers Neil , Parker Charles , Beecroft Chris , Reddy T.B.K. , Salamon Hugh , Garrity George , Fagnan Kjiersten
Published: January 2024

Increases in sequencing capacity, combined with rapid accumulation of publications and associated data resources, have increased the complexity of maintaining associations between literature and genomic data. As the volume of literature and data have exceeded the capacity of manual curation, automated approaches to maintaining and confirming associations among these resources have become necessary. Here we present the Data Citation Explorer (DCE), which discovers literature incorporating genomic data whether or not provenance was clearly indicated. This service provides advantages over manual curation methods including consistent resource coverage, metadata enrichment, documentation of new use cases, and identification of conflicting metadata. The service reduces labor costs associated with manual review, improves the quality of genome metadata maintained by the U.S. Department of Energy Joint Genome Institute (JGI), and increases the number of known publications that incorporate its data products. The DCE facilitates an understanding of JGI impact, improves credit attribution for data generators, and can encourage data sharing by allowing scientists to see how reuse amplifies the impact of their original studies.
Deciphering the molecular mechanism underlying morphology transition in two-component DNA-protein cophase separation
Authors: Li Cheng , Bian Yunqiang , Tang Yiting , Meng Lingyu , Yin Peipei , Hong Ye , Cheng Jun , Li Yuchen , Lin Jie , Tang Chao , Chen Chunlai , Li Wenfei , Qi Zhi
Published: January 2024

Nucleic acid and protein co-condensates exhibit diverse morphologies crucial for fundamental cellular processes. Despite their significance, the molecular mechanisms governing morphology transitions remain poorly understood. To address this gap in knowledge, we investigated DNA and the human transcription factor p53 as a model system, specifically focusing on DNA-protein interactive co-condensates (DPICs)—a scenario where neither dsDNA nor the protein demonstrates phase-separation behavior individually. Through a combination of experimental assays and theoretical approaches, we elucidated: (i) the phase diagram of DPICs, identifying two distinct transition phenomena—a phase transition between viscoelastic fluid and viscoelastic solid states, and a morphology transition from droplet-like to "pearl chain"-like DPICs; (ii) the growth dynamics of DPICs. Droplet-like and "pearl chain"-like DPICs, although with dramatically distinct final morphologies and material properties, share a common initial critical microscopic cluster (CMC) size at the nanometer scale during the early stage of phase separation. These findings provide novel insights into the biophysical mechanisms underlying multi-component phase separations within cellular environments.

Significance Statement

Nucleic acids and proteins have the capacity to form co-condensates, exhibiting various morphologies, including droplet-like and “pearl chains” formations. Despite this observation, the underlying biophysical mechanisms remain poorly understood. In this study, we employed DNA and the protein p53 as a model system. Our investigation revealed that the strength of the DNA-p53 interactions dictates the material properties of the co-condensates, leading to a transition from a viscoelastic fluid to a viscoelastic solid phase. This transition is accompanied by a morphological shift from droplet-like formations to structures resembling “pearl chains”. Additionally, we explored the growth dynamics of these co-condensates and demonstrated that the strength of p53-DNA interactions influences the relaxation time of the co-condensates, thereby potentially determining their morphological features.
Precision phenotyping of a barley diversity set reveals distinct drought response strategies
Authors: Paul Maitry , Dalal Ahan , Jääskeläinen Marko , Moshelion Menachem , Schulman Alan H.
Published: January 2024

Plants exhibit a wide array of responses and adaptive mechanisms to drought. During drought, the trade-off between water loss and CO2uptake for growth is mediated by the regulation of stomatal aperture in response to soil water content (SWC), among other factors. We earlier identified, in a few reference varieties of barley that differed by the SWC at which transpiration was curtailed, two divergent water use strategies: water-saving (“isohydric”) and water-spending (“anisohydric”). We proposed that an isohydric strategy may reduce risk from early droughts in climates where the probability of precipitation increases during the growing season, whereas an anisohydric strategy is consistent with environments having terminal droughts, or with those where dry periods are short and show little seasonal variation. Here, we have examined drought response in an 81-line barley diversity set that spans 20thcentury European barley breeding and identified a several lines with a third, dynamic transpirational response to drought. We found a strong positive correlation between vigor and transpiration, the dynamic group being highest for both. However, these lines curtailed daily transpiration at a higher SWC than the isohydric group. While the dynamic lines, particularly cv Hydrogen and Baronesse, were not the most resilient in terms of restoring initial growth rates, their strong initial vigor and high return to initial transpiration rates meant that their growth nevertheless surpassed more resilient lines during recovery from drought. The results will be of use for defining barley physiological ideotypes suited to future climate scenarios.
The role of chromatin state in intron retention: a case study in leveraging large scale deep learning models
Authors: Daoud Ahmed , Ben-Hur Asa
Published: January 2024

Complex deep learning models trained on very large datasets have become key enabling tools for current research in natural language processing and computer vision. By providing pre-trained models that can be fine-tuned for specific applications, they enable researchers to create accurate models with minimal effort and computational resources. Large scale genomics deep learning models come in two flavors: the first are large language models of DNA sequences trained in a self-supervised fashion, similar to the corresponding natural language models; the second are supervised learning models that leverage large scale genomics datasets from ENCODE and other sources. We argue that these models are the equivalent of foundation models in natural language processing in their utility, as they encode within them chromatin state in its different aspects, providing useful representations that allow quick deployment of accurate models of gene regulation. We demonstrate this premise by leveraging the recently created Sei model to develop simple, interpretable models of intron retention, and demonstrate their advantage over models based on the DNA langauage model DNABERT-2. Our work also demonstrates the impact of chromatin state on the regulation of intron retention. Using representations learned by Sei, our model is able to discover the involvement of transcription factors and chromatin marks in regulating intron retention, providing better accuracy than a recently published custom model developed for this purpose.
3D Bioprinting of Collagen-based Microfluidics for Engineering Fully-biologic Tissue Systems
Authors: Shiwarski Daniel J. , Hudson Andrew R. , Tashman Joshua W. , Bakirci Ezgi , Moss Samuel , Coffin Brian D. , Feinberg Adam W.
Published: January 2024

Microfluidic and organ-on-a-chip devices have improved the physiologic and translational relevance of in vitro systems in applications ranging from disease modeling to drug discovery and pharmacology. However, current manufacturing approaches have limitations in terms of materials used, non-native mechanical properties, patterning of extracellular matrix (ECM) and cells in 3D, and remodeling by cells into more complex tissues. We present a method to 3D bioprint ECM and cells into microfluidic collagen-based high-resolution internally perfusable scaffolds (CHIPS) that address these limitations, expand design complexity, and simplify fabrication. Additionally, CHIPS enable size-dependent diffusion of molecules out of perfusable channels into the surrounding device to support cell migration and remodeling, formation of capillary-like networks, and integration of secretory cell types to form a glucose-responsive, insulin-secreting pancreatic-like microphysiological system.

One-Sentence Summary

Multi-material FRESH 3D bioprinting of microfluidic CHIPS to generate fully biologic centimeter-scale and vascularized pancreatic-like tissue systems.
A learned score function improves the power of mass spectrometry database search
Authors: Ananth Varun , Sanders Justin , Yilmaz Melih , Oh Sewoong , Noble William Stafford
Published: January 2024

One of the core problems in the analysis of protein tandem mass spectrometry data is the peptide assignment problem: determining, for each observed spectrum, the peptide sequence that was responsible for generating the spectrum. Two primary classes of methods are used to solve this problem: database search andde novopeptide sequencing. State-of-the-art methods forde novosequencing employ machine learning methods, whereas most database search engines use hand-designed score functions to evaluate the quality of a match between an observed spectrum and a candidate peptide from the database. We hypothesize that machine learning models forde novosequencing implicitly learn a score function that captures the relationship between peptides and spectra, and thus may be re-purposed as a score function for database search. Because this score function is trained from massive amounts of mass spectrometry data, it could potentially outperform existing, hand-designed database search tools. To test this hypothesis, we re-engineered Casanovo, which has been shown to provide state-of-the-artde novosequencing capabilities, to assign scores to given peptide-spectrum pairs. We then evaluated the statistical power of this Casanovo score function, Casanovo-DB, to detect peptides on a benchmark of three mass spectrometry runs from three different species. Our results show that, at a 1% peptide-level false discovery rate threshold, Casanovo-DB outperforms existing hand-designed score functions by 35% to 88%. In addition, we show that re-scoring with the Percolator post-processor benefits Casanovo-DB more than other score functions, further increasing the number of detected peptides.
A drug cocktail of rapamycin, acarbose, and phenylbutyrate enhances resilience to features of early-stage Alzheimer’s disease in aging mice
Authors: Wezeman Jackson , Darvas Martin , Postupna Nadia , Klug Jenna , Mangalindan Ruby Sue , Keely Addison , Nguyen Kathryn , Johnson Chloe , Rosenfeld Manuela , Ladiges Warren
Published: January 2024

The process of aging is defined by the breakdown of critical maintenance pathways leading to an accumulation of damage and its associated phenotypes. Aging affects many systems and is considered the greatest risk factor for a number of diseases. Therefore, interventions aimed at establishing resilience to aging should delay or prevent the onset of age-related diseases. Recent studies have shown a three-drug cocktail consisting of rapamycin, acarbose, and phenylbutyrate delayed the onset of physical, cognitive, and biological aging phenotypes in old mice. To test the ability of this drug cocktail to impact Alzheimer’s disease (AD), an adeno-associated-viral vector model of AD was created. Mice were fed the drug cocktail 2 months prior to injection and allowed 3 months for phenotypic development. Cognitive phenotypes were evaluated through a spatial navigation learning task. To quantify neuropathology, immunohistochemistry was performed for AD proteins and pathways of aging. Results suggested the drug cocktail was able to increase resilience to cognitive impairment, inflammation, and AD protein aggregation while enhancing autophagy and synaptic integrity, preferentially in female cohorts. In conclusion, female mice were more susceptible to the development of early stage AD neuropathology and learning impairment, and more responsive to treatment with the drug cocktail in comparison to male mice. Translationally, a model of AD where females are more susceptible would have greater value as women have a greater burden and incidence of disease compared to men. These findings validate past results and provide the rationale for further investigations into enhancing resilience to early-stage AD by enhancing resilience to aging.