bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of MCP-1/CCR2 axis in renal fibrosis: Mechanisms and therapeutic targeting
Authors: He Shiyang , Yao Lan , Li Jun
Published: October 2023

Renal fibrosis is a common pathological manifestation in various chronic kidney diseases. Inflammation plays a central role in renal fibrosis development. Owing to their significant participation in inflammation and autoimmunity, chemokines have always been the hot spot and focus of scientific research and clinical intervention. Among the chemokines, monocyte chemoattractant protein-1 (MCP-1), also known as C-C motif chemokine ligand 2, together with its main receptor C–C chemokine receptor type 2 (CCR2) are important chemokines in renal fibrosis. The MCP-1/CCR2 axis is activated when MCP-1 binds to CCR2. Activation of MCP-1/CCR2 axis can induce chemotaxis and activation of inflammatory cells, and initiate a series of signaling cascades in renal fibrosis. It mediates and promotes renal fibrosis by recruiting monocyte, promoting the activation and transdifferentiation of macrophages. This review summarizes the complex physical processes of MCP-1/CCR2 axis in renal fibrosis and addresses its general mechanism in renal fibrosis by using specific examples, together with the progress of targeting MCP-1/CCR2 in renal fibrosis with a view to providing a new direction for renal fibrosis treatment.
Effect of age at menopause and menopause itself on high sensitivity C-reactive protein, pulse wave velocity, and carotid intima-media thickness in a Chinese population
Authors: Chen Ying , Wang Anxin , Zhang Xiaoli , Xia Fengqin , Zhao Xingquan
Published: October 2023

Potential associations between menopause, age at menopause, and clinical indicators related to cardiovascular disease (CVD) have not been elucidated. To identify the risk of CVD early and contribute to its prevention and intervention, the present study used relevant biomarkers to evaluate the risk of CVD among pre- and postmenopausal women. An overall population of 816 women (aged 40–60 y) was evaluated as premenopause, natural early menopause, or natural late menopause (ages ≤ 48 and ≥52 y), with ages 49–51 years as reference (natural menopause). High-sensitivity C-reactive protein, carotid intima-media thickness, and brachial-ankle pulse wave velocity were measured. Triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) of the postmenopausal group were each significantly higher than that of the premenopausal. However, the 3 menopausal groups were similar regarding hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. In the logistic regression model, the CRP, brachial-ankle pulse wave velocity, and carotid intima-media thickness levels were similar among the premenopause and early and late menopause groups. These results were unchanged after further adjustment for multiple confounders including age, smoking, drinking, salt intake habits, presence of hypertension, or diabetes mellitus. Menopause itself is a more important risk factor for CVD compared with menopause that begins at early or late age.
An analysis of YouTube videos about restless leg syndrome: Choosing the right guide
Authors: Tutan Duygu , Ulfberg Jan
Published: October 2023

Individuals often resort to YouTube as a means of accessing insights into their medical conditions and potential avenues for treatment. Among prevalent and incapacitating afflictions within the general populace, restless leg syndrome assumes significance. The focal objective of this investigation is to scrutinize the caliber inherent in videos pertaining to restless leg syndrome disseminated via the YouTube platform. The sorting of videos was accomplished by gauging their pertinence subsequent to conducting a search for “restless leg syndrome” on YouTube, specifically on the 20th of August, 2023. The evaluation encompassed videos curated from the selection of the top 50 English language videos deemed most relevant. The review process entailed the comprehensive assessment of relevance and content by 2 distinct medical professionals operating independently. Furthermore, pertinent descriptive attributes of each video, such as upload date, view count, likes, dislikes, and comments, were meticulously documented within the dataset. To ascertain video quality, the DISCERN Score, global quality score, and Journal of the American Medical Association rating scales were employed as evaluative tools. Significant statistical disparities were observed in terms of DISCERN scores between videos uploaded by medical doctors and those uploaded by individuals without medical qualifications (P < .001). Correspondingly, upon comparing the 2 aforementioned groups, videos uploaded by healthcare professionals exhibited statistically superior quality scores in both the Journal of the American Medical Association and global quality score assessments (P < .001 for both comparisons). The informational quality regarding restless leg syndrome on YouTube presents a spectrum of variability. Notably, videos that offer valuable insights, as well as those that could potentially mislead viewers, do not display discernible variations in terms of their viewership and popularity. For patients seeking reliable information, a useful and safe approach involves favoring videos uploaded by medical professionals. It is imperative to prioritize the professional identity of the content uploader rather than being swayed by the video’s popularity or the quantity of comments it has amassed.
Is there a weekend effect in spine surgery?: A systematic review and meta-analysis of postoperative outcomes
Authors: Chang Yu , Hsu Heng-Juei , Hsu Hao-Hsiang , Wong Chia-En , Chi Kuan-Yu , Lee Po-Hsuan , Huang Chi-Chen , Lee Jung-Shun , Chen Chien-Min
Published: October 2023

Background:

The concept of a weekend effect is that patients admitted to hospitals on the weekend tend to have poorer outcomes compared to those admitted on a weekday. Whether there is a weekend effect among patients receiving spine surgery is not well described in the literature. We sought to perform a systematic review with meta-analysis to explore whether a weekend effect exists among patients experiencing spinal surgery.

Methods:

The Cochrane Library, PubMed, Embase, and MEDLINE electronic databases were searched for relevant articles. Meta-analyses were performed using functions available in the metafor package within the R software. We obtained adjusted odds ratios (OR) from included studies and pooled OR through an inverse variance method. A random-effects model was applied for meta-analysis and effect sizes were presented with their corresponding 95% confidence intervals (CI).

Results:

Our search strategy identified 316 references from electronic databases and eventually 6 studies were included in the analysis. The pooled result of 5 studies reporting overall complication rate indicated significant increased risk of complications among the weekend admission group (OR, 1.35; 95% CI, 1.01 to 1.80). The pooled results of 3 studies demonstrated no difference in overall mortality rates between these 2 groups of patients (OR, 1.18; 95% CI, 0.67 to 1.97).

Conclusions:

In spinal surgical patients, the weekend effect significantly contributes to a higher complication rate. Knowledge of potential adverse events in patients admitted on weekends is necessary for spinal surgeons and caregivers to improve patient outcomes with spinal surgery.
Intravenous high-dose vitamin C monotherapy for sepsis and septic shock: A meta-analysis of randomized controlled trials
Authors: Zeng Yiqian , Liu Zhao , Xu Fei , Tang Zhanhong
Published: October 2023

Background:

Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis.

Methods:

The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models.

Results:

Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality.

Conclusion:

These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.
Plethysmographic variability index and perfusion index in patients with axillary brachial plexus nerve catheters: An observational study
Authors: Aksu Hale , Ocmen Elvan , Omur Dilek , Kizil Sezin , Karci Ayse
Published: October 2023

Axillary nerve blocks are commonly using for forearm and hand surgery. Especially for finger replacement it has been shown continuous plexus blockade improves microcirculation. Addition to that benefit continuous blockade provides adequate analgesia. In this study perfusion index (PI) and plethysmographic variability index (PVI) changes were used to evaluate in blocks success. The PVI and PI values were detected by a Radical-7TM finger pulse oximetry device (Massimo Corp, USA) in both fingers of 50 plastic surgery patients, who received an axillary brachial plexus catheter before surgery. Data recorded at baseline, during catheter replacement, after catheter replacement, and before surgery. All periods hemodynamic data, visual analog scala, Ramsey sedation score and patient satisfaction score were collected. In all 110 patients blocks were successfully applied, PI values in blocked arm increased after local analgesic application (during catheter replacement), (P < .05), PVI values were decreased in the same period but there were no statistical significance. The PI increases after peripheral plexus blockade and may be used as an indicator for successful block placement in awake patient. And also, it may be used as an indicator for catheter effectiveness after surgery. But PVI values cannot detect that kind of relation with nerve blockade.
Molybdenum target mammography-based prediction model for metastasis of axillary sentinel lymph node in early-stage breast cancer
Authors: Yuan Caixing , Xu Guolin , Zhan Xiangmei , Xie Min , Luo Mingcong , She Lilan , Xue Yunjing
Published: October 2023

Sentinel lymph node (SLN) status is closely related to axillary lymph node metastasis in breast cancer. However, SLN biopsy has certain limitations due to invasiveness and diagnostic efficiency. This study aimed to develop a model to predict the risk of axillary SLN metastasis in early-stage breast cancer based on mammography, a noninvasive, cost-effective, and potential complementary way. Herein, 649 patients with early-stage breast cancer (cT1–T2) who received SLN biopsy were assigned to the training cohort (n = 487) and the validation cohort (n = 162). A prediction model based on specific characteristics of tumor mass in mammography was developed and validated with R software. The performance of model was evaluated by receiver operating characteristic curve, calibration plot, and decision curve analysis. Tumor margins, spicular structures, calcification, and tumor size were independent predictors of SLN metastasis (all P < .05). A nomogram showed a satisfactory performance with an AUC of 0.829 (95% CI = 0.792–0.865) in the training cohort and an AUC of 0.825 (95% CI = 0.763–0.888) in validation cohort. The consistency between model-predicted results and actual observations showed great Hosmer–Lemeshow goodness-of-fit (P = .104). Patients could benefit from clinical decisions guided by the present model within the threshold probabilities of 6% to 84%. The prediction model for axillary SLN metastasis showed satisfactory discrimination, calibration abilities, and wide clinical practicability. These findings suggest that our prediction model based on mammography characteristics is a reliable tool for predicting SLN metastasis in patients with early-stage breast cancer.
A retrospective study of nonneoplastic and neoplastic disorders of the salivary glands
Authors: Vamesu Sorin , Ursica Oana Andreea , Gurita Ana Maria , Voda Raluca Ioana , Deacu Mariana , Aschie Mariana , Bosoteanu Madalina , Cozaru Georgeta Camelia , Mitroi Anca Florentina , Orasanu Cristian Ionut
Published: October 2023

The spectrum of major and minor salivary gland disorders varies widely. Epidemiological data on some injury categories are rare and often not up-to-date. This study aims to analyze epidemiological data using clinical, paraclinical, and histopathological parameters. Study was carried out for 5 years on the nonneoplastic and tumoral pathology of the salivary glands. Data were statistically analyzed using the appropriate parameters. Data analysis according to the biological behavior of the lesions revealed great heterogeneity. Statistically significant correlations were observed between the type of injury, age (P = .002) and gender (0.033). The environment of origin of the patients as well as the comorbidities reflected in most cases the nature of the process. Associations were also observed between the biological behavior of the lesions and the hemicranial topography (P = .019), the type of salivary gland (P = .024), and the surgical technique used (P < .001). Most cases were identified in the major salivary glands, often in the parotid. The most common diseases are represented by nonspecific chronic sialadenitis (nonneoplastic lesion), pleomorphic adenoma and Warthin tumor (benign tumors), mucoepidermoid carcinoma (malignant tumor), and squamous carcinoma (secondary tumor). They presented axial diameters between 2 to 95 mm. The most used curative technique was subtotal excision with facial nerve preservation. In conclusion, the study highlighted the main epidemiological aspects of salivary gland disorders. Some data agree with the specialty literature, and particular aspects are also observed. Therefore, this research is useful both in the medical and research fields.
Assessing attentional task-related electroencephalogram signal variations by using mobile electroencephalogram technology: An experimental study
Authors: Matsuo Moemi , Higuchi Takashi , Miyabara Hiroya , Higashijima Misako , Oshikawa Takeshi , Nakamura Masatoshi , Yamaguchi Yuji , Higashionna Takuya
Published: October 2023

Background:

A better understanding of the network responses of cortical activities during rest and cognitive tasks is necessary. Therefore, in this study, we aimed to evaluate cerebral activities during attentional tasks by using mobile electroencephalography, identifying the types of attentional components and brain waves.

Methods:

In this experimental study, we enrolled 12 healthy young adults. The attentional tasks comprised parts A and B of the Trail-Making Test (TMT). Nineteen electroencephalography electrodes were placed over various brain regions. The Wilcoxon signed-rank test was used to examine the differences in power levels between the rest and TMT conditions.

Results:

During TMT part A, the electroencephalography power level of the delta waves was significantly higher in the right frontal, left central, left occipital, left inferior frontal, right mid-temporal, right posterior temporal, and middle parietal areas (P < .05) than those during the resting state; that of the alpha waves was significantly lower in the left posterior temporal area (P = .006); and that of the high gamma waves was significantly lower in the left parietal (P = .05) and left occipital (P = .002) areas. During TMT part B, the electroencephalography power level of the beta waves was significantly higher in the right frontal area (P = .041) than that during the resting state, and that of the low gamma waves was significantly higher in the left frontal pole, right frontal, and right inferior frontal areas (P < .05). During the focused attentional task, the power level of the delta waves increased and that of the alpha waves decreased, and during the alternating attentional task, those of both the beta and gamma waves increased. The delta waves were related to the whole brain, the alpha and high gamma waves to the left posterior lobe, and the beta and low gamma waves to both frontal lobes.

Conclusion:

These findings contribute to the basic knowledge necessary to develop new attentional assessment methods for clinical situations.
The Effects of Organizational Characteristics, Individual Nurse Characteristics, and Occupational Fatigue on Missed Care at Night
Authors: Crincoli Suzanne , de Cordova Pamela , Thomas-Hawkins Charlotte , Flynn Linda , Zha Peijia , Sagherian Knar
Published: October 2023

Background

Missed care is defined as the omission or delay of necessary patient care and is internationally reported by nurses as a significant safety risk. Nurses working at night also report high levels of occupational fatigue that, coupled with inadequate staffing and practice environment support, may impede a nurse’s ability to carry out the nursing process and lead to more missed care.

Objective

The study’s objective was to examine the interrelationships among organizational and nurse characteristics, occupational fatigue, and missed care among nurses working at night.

Methods

A cross-sectional design was used. Participants included registered nurses (RNs) who worked at night in New Jersey acute care hospitals. Multiple linear regression and simple moderation analyses were performed to examine the associations.

Results

Nurses reported missing necessary care at night. Unsupportive practice environments, high RN workloads, high patient–RN ratios, high chronic fatigue levels, and low intershift recovery were individually associated with missed care at night. High patient-to-RN ratios and chronic fatigue were independently associated with missed care. However, patient-to-registered-staffing levels had the most considerable effect on missed care at night. Nurses’ years of experience and the number of hours of sleep between shifts were significant moderators of the relationship between occupational fatigue states and missed care.

Discussion

This study is the first to examine the interrelationship between occupational fatigue levels, organizational and nurse characteristics, and missed care at night. There is an urgent need to implement strategies in hospital organizations that foster work schedules and adequate staffing patterns that lessen nurses’ occupational fatigue levels to ensure our workforce’s and patients’ safety.
Hospital Environmental Disruptors and Caregiver Sleep During Hospitalization
Authors: Fernández-Puerta Laura , Prados Germán , Quiñoz-Gallardo María Dolores , Vellido-González Dolores , González-Guerrero María Leticia , Rivas-Campos Antonio , Jiménez-Mejías Eladio
Published: October 2023

Purpose

Caregivers must cope with a poor sleep environment when caring for someone admitted to the hospital. The aim was to study the environmental factors associated with a sleep disruption pattern in caregivers during hospitalization and to test their association with caregivers' insomnia symptoms.

Design

This was a cross-sectional study.

Methods

One hundred twenty-three caregivers completed the study. The effect of environmental stimuli on sleep disruption was measured on a scale from 1 to 10 (1 = no disruption, 10 = significant disruption). Type of room (single vs shared), insomnia symptoms, anxiety and depression, and patients' dependence (Barthel Index) were assessed as well. Caregiver and patient characteristics as well as identified hospital disruptors were compared with Student t test, χ
2 test, and Fisher exact test according to the caregivers' type of room. A linear regression model using main caregiver and patient sociodemographic variables, questionnaires, and the sum of all hospital disruptors determined the factors associated with caregivers' insomnia symptoms.

Results

Of the caregivers and their care recipients, 51.2% shared a room with 1 to 2 other patients. Higher self-reported levels of sleep disruption due to environmental stimuli were found in shared rooms when compared with single rooms (eg, nursing care, noise, and light) (P < .05). Hospital sleep disruptors (adjusted regression coefficient, 0.15; 95% confidence interval, 0.06–0.24) and caregiver anxiety (adjusted regression coefficient, 0.57; 95% confidence interval, 0.33–0.81) were predictors for insomnia (P < .01). However, caregivers' type of room was not associated with insomnia severity symptoms (P > .05).

Conclusions

Interventions are urgent to implement, such as relieving caregivers from patient needs during the night, providing them with single rooms, and conducting multiple nursing tasks in 1 visit to minimize night hospital noise.
Arginase-1 is More Specific Than Hepatocyte Paraffin 1 for Differentiating Hepatocellular Carcinomas with Cytoplasmic Clearing from Nonhepatocellular Clear Cell Tumors in Liver Biopsies
Authors: Larson Brent K. , Dhall Deepti , Guindi Maha
Published: October 2023

Arginase-1 (Arg1) and hepatocyte paraffin antigen 1 (HepPar1) are specific and sensitive markers of hepatocellular differentiation. HepPar1 is a granular cytoplasmic immunostain that may be negative in hepatocellular carcinoma (HCC) with cytoplasmic clearing. Arg1 shows uniform cytoplasmic positivity and frequent nuclear positivity. This study was undertaken to determine the staining pattern of Arg1 in HCC with cytoplasmic clearing and compare its use to HepPar1. Fifteen resected HCCs with cytoplasmic clearing and 31 biopsies of clear cell liver tumors (14 HCCs and 17 nonhepatocellular tumors) were identified. Resections were stained with Arg1 to characterize the pattern, intensity, and extent of Arg1 positivity. Biopsies were stained with Arg1 (n=31) and HepPar1 (n=28). In all, 13/15 resected and 11/14 biopsied HCCs with cytoplasmic clearing showed nuclear positivity for Arg1. Both Arg1 and HepPar1 stained significantly more HCCs than nonhepatocellular tumors (13/14 and 11/12, respectively, with P<0.0001 and P=0.0018, respectively). However, HepPar1 stained significantly more nonhepatocellular tumors (5/12) than Arg1 (0/17, P=0.0445). Arg1 frequently displayed nuclear positivity, and interobserver agreement was better for Arg1 (K=0.93 vs. 0.79). Overall, Arg1 is more specific than HepPar1 for differentiating HCC with cytoplasmic clearing from nonhepatocellular clear cell tumors in the liver. Its staining characteristics, including nuclear positivity, make it easier to interpret in combination with morphology, improving interobserver variability, and it stains significantly fewer mimics than HepPar1.
Hepatitis B surface antigen loss in individuals with chronic hepatitis B virus and HIV-1 infections in Botswana
Authors: Mpebe Gorata G.A. , Phinius Bonolo B. , Mutenga Sharon , Baruti Kabo , Bhebhe Lynnette , Choga Wonderful T. , Jongman Mosimanegape , Pretorius-Holme Molly , Gaolathe Tendani , Mmalane Mompati , Shapiro Roger , Makhema Joseph , Lockman Shahin , Moyo Sikhulile , Anderson Motswedi , Gaseitsiwe Simani
Published: October 2023

Objectives:

We sought to determine hepatitis B surface antigen (HBsAg) loss and its predictors among people with chronic hepatitis B (CHB) infections and HIV (PWH) in Botswana.

Methods:

Archived plasma samples from a cohort of PWH in Botswana (2013–2018) with 3 yearly time-points were used. Samples were screened for HBsAg, immunoglobulin M HBV core antibodies (anti-HBc IgM) and HBV e-antigen (HBeAg) at all time points. HBV deoxyribonucleic acid (DNA) quantification was done at baseline. The Wilcoxon rank-sum was used to compare continuous variables while the chi-squared test and Fishers exact test were used for categorical data wherever appropriate. Logistic regression was used to assess predictors of seroclearance.

Results:

Of 141 participants with HBsAg-positive serology (HBsAg+) at baseline, 92.2% (131/141) [95% confidence interval (CI) 87.4–96.1] were persistently HBsAg+ at year 1. We report a HBsAg loss of 7.1% (10/141) (95% CI 3.9–12.6) among participants with negative HBeAg and negative IgM serologies. HBsAg loss was 6.3% (7/111) among antiretroviral therapy (ART)-experienced participants and 10.7% (3/28) (95% CI 0.4–5.0) in ART-naive participants. Most participants who had positive anti-HBc IgM serology and did not lose HBsAg were on either lamivudine (3TC)-based therapy or non-tenofovir disoproxil fumarate (TDF)-based therapy, except for one participant. The participants also had varying HBeAg status. HBsAg loss was independent of HIV viral load, CD4+ cell count, age, and sex.

Conclusion:

We report a HBsAg loss of 6.3% over a 3-year period among ART-experienced CHB participants. Future studies that focus on HBsAg loss in mono-infected patients and the possible correlation between HBeAg status and HBsAg loss are warranted.
1RM Living
Authors: Jones Dustin
Published: October 2023

1 Rep Max (1RM) Living occurs when the demands of life are near or exceeding one's capacity. This situation can be troublesome and relatively urgent for many. Telerehabilitation offers some barriers but also opportunities to helping people in this common situation. This article discusses the importance of 1RM Living, how to identify, and how we can destroy 1RM Living to change our patients' lives for the better.
Racial Disparity among Youth Decedents of Legal Intervention Trauma
Authors: Yu Peter T , Goodman Laura F , Riley John S , Giron Annie , Guner Yigit S , Peranteau William H , Schomberg John
Published: October 2023

BACKGROUND:

Legal intervention trauma (LIT) is defined as injury due to any encounter with law enforcement. This study investigates associations between demographics, violent status, and law enforcement tactics among youth decedents of LIT.

STUDY DESIGN:

Decedents of LIT age 26 years or younger were identified using the CDC’s National Violent Death Reporting System from 2003 to 2018. Decedents were classified as “violent” if they possessed a weapon, were committing a violent crime, or if law enforcement reported justified use of force. All others were classified as “nonviolent.” Law enforcement tactics were stratified into “lethal” (firearm with standard ammunition) or “less lethal” (any other) force. Differences in the racial distribution across these classifications were assessed using chi-square tests of proportions.

RESULTS:

We identified 1,281 youth decedents of LIT; of which, 92.5% met violent criteria. Black youths were less likely than White youths to possess a weapon (71.6% vs 77.4%, p = 0.02) and were not more likely to be committing a violent crime (63.6% vs 60.4%, p = 0.27). They were, however, more likely than White youths to experience force reported as justified by law enforcement (89.9% vs 82.4%, p = 0.002) and to experience exclusively lethal force not preceded by less-lethal tactics (94.0% vs 88.7%, p = 0.001). Among the subset of 85 cases where law enforcement reported justified use of force despite the decedent not possessing a weapon or committing a violent crime, the precipitating event was more often a traffic stop for Black youths than for White youths (28.5% vs 6.66%, p = 0.02).

CONCLUSIONS:

These findings indicate a racial disparity among youth decedents of LIT.
Bayesian inference of relative fitness on high-throughput pooled competition assays
Authors: Razo-Mejia Manuel , Mani Madhav , Petrov Dmitri
Published: October 2023

The tracking of lineage frequencies via DNA barcode sequencing enables the quantification of microbial fitness. However, experimental noise coming from biotic and abiotic sources complicates the computation of a reliable inference. We present a Bayesian pipeline to infer relative microbial fitness from high-throughput lineage tracking assays. Our model accounts for multiple sources of noise and propagates uncertainties throughout all parameters in a systematic way. Furthermore, using modern variational inference methods based on automatic differentiation, we are able to scale the inference to a large number of unique barcodes. We extend this core model to analyze multi-environment assays, replicate experiments, and barcodes linked to genotypes. On simulations, our method recovers known parameters within posterior credible intervals. This work provides a generalizable Bayesian framework to analyze lineage tracking experiments. The accompanying open-source software library enables the adoption of principled statistical methods in experimental evolution.
Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
Authors: Shu Daniel H. , Ho Won Jin , Kagohara Luciane T. , Girgis Alexander , Shin Sarah M. , Danilova Ludmila , Lee Jae W. , Sidiropoulos Dimitrios N. , Mitchell Sarah , Munjal Kabeer , Howe Kathryn , Bendinelli Kayla J. , Qi Hanfei , Mo Guanglan , Montagne Janelle , Leatherman James M. , Lopez-Vidal Tamara Y. , Zhu Qingfeng , Huff Amanda L. , Yuan Xuan , Hernandez Alexei , Coyne Erin M. , Zaidi Neeha , Zabransky Daniel J. , Engle Logan L. , Ogurtsova Aleksandra , Baretti Marina , Laheru Daniel , Durham Jennifer N. , Wang Hao , Anders Robert , Jaffee Elizabeth M. , Fertig Elana J. , Yarchoan Mark
Published: October 2023

Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal of the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like structures that can arise within tumors, may contribute to the establishment of immunological memory in this setting, but understanding of their role remains limited. Here, we investigated the contribution of TLS to antitumor immunity in hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy. We found that neoadjuvant immunotherapy induced the formation of TLS, which were associated with superior pathologic response, improved relapse free survival, and expansion of the intratumoral T and B cell repertoire. While TLS in viable tumor displayed a highly active mature morphology, in areas of tumor regression we identified an involuted TLS morphology, which was characterized by dispersion of the B cell follicle and persistence of a T cell zone enriched for ongoing antigen presentation and T cell-mature dendritic cell interactions. Involuted TLS showed increased expression of T cell memory markers and expansion of CD8+cytotoxic and tissue resident memory clonotypes. Collectively, these data reveal the circumstances of TLS dissolution and suggest a functional role for late-stage TLS as sites of T cell memory formation after elimination of viable tumor.

Graphical Abstract

Highlights

In patients with hepatocellular carcinoma (HCC), tertiary lymphoid structures (TLS) are induced by neoadjuvant immunotherapy and are associated with favorable clinical outcomes.

TLS within the same tumor demonstrate extensive sharing of expanded granzyme K and granzyme B-expressing CD8+T effector memory clonotypes, but the B cell repertoires of individual TLS are almost wholly distinct, consistent with independent germinal center reactions.

Within areas of viable tumor, mature TLS are characterized by high expression of CD21 and CD23, BCL6+germinal center B cells, and close interactions between DCLAMP+mature dendritic cells and CXCR5-CXCR3+CD4 T peripheral helper cells within a T cell zone adjacent to the B cell follicle.

Within areas of tumor regression, an involuted TLS morphology is identified that is notable for dissolution of the B cell germinal center, retention of the T cell zone, and increased T cell memory.
Vicious cycle of hemodynamic perturbation and endothelial injury in development and progression of pulmonary arterial hypertension
Authors: Deng Yupu , Chaudhary Ketul R. , Yang Anli , Kesavan Kirishani , Wang Liyuan , Chathely Kevin , Stewart Duncan J.
Published: October 2023

Background

Pulmonary arterial hypertension (PAH) is a devastating disease caused by loss of effective lung microvasculature for which there is no curative treatment. Evidence from preclinical models and human disease-causing genetic mutations point to endothelial cell (EC) injury and apoptosis as a central trigger for the initiation of PAH. However, how EC apoptosis leads to pulmonary hypertension (PH) and complex arteriolar remodeling is uncertain.

Methods

Rats were subjected to SU5416-hypoxia (SUHx) and EC apoptosis, pulmonary vascular remodeling and arterial volume was assessed by immunohistochemistry, histology and microCT, respectively. Left pulmonary artery banding (LPAB) was performed, either 1 week before (prevention) or 5 weeks after SU injection (reversal), to study the effect of hemodynamic offloading.

Results

In the SUHx model, EC apoptosis was markedly increased as early as 3 days post-SU, persisting through PAH development, and this was associated with a profound arterial pruning with reduction in lung arterial volume (∼80%). LPAB abrogated lung EC apoptosis in the banded left lung and prevented as well as reversed arteriolar pruning. Moreover, in the reversal protocol, removal of the band at 10 weeks resulted in improvement in pulmonary hemodynamics and RV function at 13 weeks.

Conclusion

These data demonstrate that perturbed hemodynamic factors triggered by lung microvascular arteriolar loss play a requisite role in perpetuating endothelial injury in experimental PAH, leading to persistent arterial EC injury and disease progression. Importantly, vascular loss, arterial remodeling and PH are reversible once the cycle of perturbed hemodynamics and EC injury is broken by unilateral lung banding.
Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer’s disease
Authors: Liu Chang , Cardenas-Rivera Alfredo , Teitelbaum Shayna , Birmingham Austin , Alfadhel Mohammed , Yaseen Mohammad A.
Published: October 2023

Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer’s disease (AD). Numerous studies have asserted a close association between neuroinflammation and disrupted cerebral energetics. During AD progression and other neurodegenerative disorders, a persistent state of chronic neuroinflammation reportedly exacerbates cytotoxicity and potentiates neuronal death. Here, we assessed the impact of a neuroinflammatory challenge on metabolic demand and microvascular hemodynamics in the somatosensory cortex of an AD mouse model. We utilized in vivo 2-photon microscopy and the phosphorescent oxygen sensor Oxyphor 2P to measure partial pressure of oxygen (pO2) and capillary red blood cell flux in cortical microvessels of awake mice. Intravascular pO2 and capillary RBC flux measurements were performed in 8-month-old APPswe/PS1dE9 mice and wildtype littermates on days 0, 7, and 14 of a 14-day period of lipopolysaccaride-induced neuroinflammation. Before the induced inflammatory challenge, AD mice demonstrated reduced metabolic demand but similar capillary red blood cell flux as their wild type counterparts. Neuroinflammation provoked significant reductions in cerebral intravascular oxygen levels and elevated oxygen extraction in both animal groups, without significantly altering red blood cell flux in capillaries. This study provides evidence that neuroinflammation alters cerebral oxygen demand at the early stages of AD without substantially altering vascular oxygen supply. The results will guide our understanding of neuroinflammation’s influence on neuroimaging biomarkers for early AD diagnosis.
A Bond-Anchored Network Structure Alignment (BANSA) Method for Graphical Analysis of Protein-Protein Interfacial Regions
Authors: Tam Justin , Chen Brian Y.
Published: October 2023

We introduce a method to analyze and compare intermolecular bonds formed between protein-protein interactions. Utilizing the DiffBond software, we calculate potential intermolecular bonds, such as ionic bonds, hydrogen bonds, and salt bridges, based on amino acid structural and spatial parameters. This results in a graphical representation of bonds termed a bond network for each protein pair interaction. We then introduce an innovative strategy, the Bond-anchored Network Structural Alignment (BANSA), to align these networks using bond formation as anchor points. This alignment process uses the Root Mean Square Deviation (RMSD) to quantitatively assess the similarity between molecular structures. We validate the BANSA approach using several forms of analysis including a heatmap analysis, which provides a consolidated view of the entire bond network as well as a thorough comparison with existing literature. The results highlight the method’s potential to offer insights into molecular interactions across various protein pairs without a need for direct modelling of protein-protein interactions.
Glucocorticoid intermittence coordinates rescue of energy and mass in aging-related sarcopenia through the myocyte-autonomous PGC1alpha-Lipin1 transactivation
Authors: Prabakaran Ashok Daniel , McFarland Kevin , Miz Karen , Durumutla Hima Bindu , Piczer Kevin , Soussi Fadoua El Abdellaoui , Latimer Hannah , Werbrich Cole , Blair N. Scott , Millay Douglas P , Prideaux Brendan , Finck Brian N , Quattrocelli Mattia
Published: October 2023

Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels muscle metabolism based on frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone rescued muscle quality in aged 24-month-old mice to levels comparable to young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing PGC1alpha and its co-factor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1alpha, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed the myocyte-specific Lipin1 as non-redundant factor coaxing PGC1alpha upregulation to the stimulation of both oxidative and anabolic capacities. Our study unveils an aging-resistant druggable program in myocytes to coordinately rescue energy and mass in sarcopenia.
Root Ions Fluxes and Osmolarity Changes in Grass Species Differing in Salinity Tolerance
Authors: Wang Liping , Elzenga Theo , Staal Marten
Published: October 2023

Agricultural areas are increasingly being affected by salt due to irrigation practices and rising levels of salty groundwater. Different plant species have varying degrees of sensitivity to salinity and employ distinct mechanisms to avoid severe damage caused by salt stress. We compared three grass species with different ecological backgrounds, namelyLolium perenne, Festuca rubra, andPuccinellia maritima, in terms of their ability to maintain growth when exposed to salt stress, the extent of Na+-induced K+efflux, and the accumulation of salts in their shoots. Our results demonstrate that the changes in K+and H+fluxes at the root tip induced by NaCl exposure are correlated with the salt tolerance characteristics of these grass species. Specifically,L. perenneexhibited the highest leakage of K+from its roots, the highest accumulation of Na+in its shoots, and the lowest shoot growth under salt stress. On the other hand,P. maritimashowed minimal changes in ion fluxes in response to salinity stress.P. maritimamaintained the lowest contribution of Na+to the total osmolarity in its shoots and exhibited the least detrimental effect of salt on shoot dry matter. The root cortex including the exodermis and endodermis could be one of the benefit barriers that help defense against salts. In conclusion, root ions fluxes and osmolarity changes in grass species have different salinity tolerance of plants from various habitats. The salt resistance plants restrict leakage of K and exclude Na more effectively. Overall, these results broadened our knowledge of salt resistance in grass species.
Healthy ageing influences how the shape of alpha and beta oscillations change during reaction time tasks
Authors: Opie George M , Hughes James M , Puri Rohan
Published: October 2023

Age-related changes to the power and frequency of the brains oscillatory activity have been reported by an extensive literature. In contrast, the influence of advancing age on theshapeof oscillation waveforms, a characteristic with increasingly recognised physiological and functional relevance, has not been previously investigated. To address this, we examined the shape of alpha and beta band oscillations from electroencephalography (EEG) data recorded during performance of simple and go/no-go reaction time tasks in 33 young (23.3 ± 2.9 years, 27 females) and 27 older (60.0 ± 5.2 years, 23 females) adults. The shape of individual cycles was characterised using instantaneous frequency, and then decomposed into waveform motifs using principal component analysis. This analysis identified four principal components (one from the alpha band, 3 from the beta band) that were uniquely influenced by the different motor tasks and/or age. These each described different dimensions of shape and tended to be modulated during the reaction phase of each task. However, the way in which each facet of shape varied during the task was unrelated to motor performance, indexed via reaction time, in either group or band. Our results suggest that although oscillation shape is task-dependent, the nature of this effect is altered by advancing age. While these outcomes demonstrate the utility of this approach for understanding the neurophysiological effects of ageing, future work that more clearly links these outcomes with function will be critical.
Life history traits mediate elevational adaptation in a perennial alpine plant
Authors: Pålsson Aksel , Walther Ursina , Fior Simone , Widmer Alex
Published: October 2023

Spatially divergent natural selection drives adaptation to contrasting environments and the evolution of ecotypes. Understanding this process in perennial plants is challenging because natural selection acts on multiple life history traits linked by fitness trade-offs.

In a multi-year reciprocal transplant experiment of high and low elevation populations of the alpine carnationDianthus carthusianorumin the Central Alps, we tested how different stages of the life cycle contribute to adaptation. Moreover, we used matrix population models to infer the specific contributions of individual life stages to fitness, coupled with trade-off analyses.

We found genotype x environment interactions consistent with elevational adaptation both in single fitness components linked to reproduction and survival, and in integrative fitness estimates. Adaptation at low elevation is driven by early reproduction, in contrast to an opposite strategy at high elevation. Adaptive life-history differences between populations originating from low and high elevations are mediated by environmental effects on plant growth and trade-offs between reproduction and survival.

Our work reveals elevational ecotypes of the perennial alpine plantD. carthusianorumthat express alternative life history strategies in response to climatic differences shaping resource allocation.
Discarded sequencing reads uncover natural variation in pest resistance inThlaspi arvense
Authors: Galanti Dario , Jung Jun Hee , Müller Caroline , Bossdorf Oliver
Published: October 2023

Understanding the genomic basis of natural variation in plant pest resistance is an important goal in plant science, but it usually requires large and labour-intensive phenotyping experiments. Here, we explored the possibility that non-target reads from plant DNA sequencing can serve as phenotyping proxies for addressing such questions. We used data from a whole-genome and -epigenome sequencing study of 207 natural lines of field pennycress (Thlaspi arvense) that were grown in a common environment and spontaneously colonized by aphids, mildew and other microbes. We found that the numbers of non-target reads assigned to the pest species differed between populations, had significant SNP-based heritability, and were associated with climate of origin and baseline glucosinolates content. Specifically, pennycress lines from cold and thermally fluctuating habitats, presumably less favorable to aphids, showed higher aphid DNA load, i.e. decreased aphid resistance. Genome-wide association analyses identified genetic variants at known defense genes but also novel genomic regions associated with variation in aphid and mildew DNA load. Moreover, we found several differentially methylated regions associated with pathogen loads, in particular differential methylation at transposons and hypomethylation in the promoter of a gene involved in stomatal closure, likely induced by pathogens. Our study provides first insights into the defense mechanisms ofThlaspi arvense, a rising crop and model species, and demonstrates that non-target whole genome sequencing reads, usually discarded, can be leveraged to estimate intensities of plant biotic interactions. With rapidly increasing numbers of large sequencing datasets worldwide, this approach should have broad application in fundamental and applied research.
An “alert state” ribosome population acts as a master regulator of cytokine-mediated processes
Authors: Dopler Anna , Alkan Ferhat , Malka Yuval , Hoefakker Kelly , Isaeva Olga I. , Kerkhoff Mandy , Gangaev Anastasia , Silva Joana , Ramalho Sofia , Hoekman Liesbeth , Altelaar Maarten , van der Kammen Rob , Yewdell Jonathan Wilson , Kvistborg Pia , Faller William James
Published: October 2023

Inflammatory cytokines are pivotal to immune responses. Upon cytokine exposure, cells enter an “alert-state” that enhances their visibility to the immune system. Here, we identified an “alert-state” subpopulation of ribosomes (ASRs) defined by the presence of the P-stalk. We show that ASRs are formed in response to cytokines linked to tumor immunity, and are involved in the preferential translation of mRNAs vital for the cytokine response.

Mechanistically, ASRs are required for the efficient translation of transmembrane domains of receptor molecules involved in cytokine-mediated processes. Importantly, loss of the ASR prevents CD8+ T cell recognition and killing, and inhibitory cytokines like TGFβ hinder ASR formation, suggesting that the ASR is a central regulatory hub upon which multiple signals converge. Thus, the ASR is an essential mediator of the cellular rewiring that occurs following cytokine exposure, via the translational regulation of this process.