bluuebunny/crossref_metadata_2025 huggingface dataset:
Achievements of international rare cancers networks and consortia in the neuro-oncology field
Authors: Di Nunno Vincenzo , Franceschi Enrico , Idbaih Ahmed
Published: September 2024

Purpose of review

In this review, we investigated the role of European oncological networks on management and care of patients with central nervous system (CNS) malignancies.

Recent findings

Within this universe of tumors, malignancies of the central nervous system (CNS) malignancies represent a challenge because of several reasons such as biological complexity, the need of dedicated experienced physicians (surgeons, pathologists, radiologists and neuro-oncologists) and tertiary healthcare providers. Limits to the development of effective and innovative care are represented by the rarity of these tumors and their extreme heterogeneity in terms of clinical presentation, course of the disease, genetic assessments and site of presentation. The oncological networks are societies or associations, which make possible to connect patients, scientists, doctors and researchers together allowing to obtain several improvements.

Oncological networks can cooperate to increase accrual rate and speed in clinical trials, share data about CNS malignancy management and improve knowledge toward this class of tumors within patients and health operators promoting equity and high standard of care.
Revision Endoscopic Carpal Tunnel Release: An Update on Technique and Outcomes
Authors: Ratigan Conor M. , Yocum Derek S. , Fuller Sam M.
Published: September 2024

Background:

Carpal tunnel release is among the most frequently conducted upper extremity procedures. While it typically provides patients with improved sensation, decreased pain, and improved function, a small percentage of cases require revision due to failed initial surgery. Consequently, adoption of endoscopic techniques for carpal tunnel revision procedures is beginning to be explored.

Methods:

A retrospective analysis was conducted of postoperative clinical visits and patient-reported outcome measures for four patients who had undergone five endoscopic revision carpal tunnel release procedures (one patient had bilateral disease). All five cases had symptoms consistent with recurrent carpal tunnel syndrome.

Results:

One hundred percent (5 of 5) of cases resulted in patients reporting symptom improvement. Postoperative clinical visits and improved patient-reported outcome measures (QuickDash, PROMIS Upper Extremity, VAS Pain, PSEQ, PHQ, and Surgery Satisfaction) scores from baseline to 6 weeks demonstrated successful postoperative function and symptom resolution. Five of five cases resulted in patients resuming normal activities without restrictions within 1–5 weeks, with an average of 3.4 weeks.

Conclusions:

Preliminary findings suggest the endoscopic revision procedure may be safe and effective for patients with recurrent carpal tunnel syndrome, extending the indications to include scars proximal to the wrist crease. Moreover, this minimally invasive procedure facilitates a transition back to normal activities and avoids incisions on weight-bearing surfaces of the palm. Adopting endoscopic revision may reduce the need for prolonged postoperative care and physical therapy. However, due to the limited sample size of five patients, further investigation with larger cohorts is warranted to confirm these observations.
Aortic reservoir-excess pressure parameters are associated with worse cognitive function in people with untreated stage II/III hypertension
Authors: Aizawa Kunihiko , Jordan Andrew N. , Gooding Kim M. , Llewellyn David J. , Mawson David M. , Casanova Francesco , Gates Phillip E. , Adingupu Damilola D. , Elyas Salim , Hope Suzy V. , Gilchrist Mark , Strain W. David , Clark Christopher E. , Bellenger Nicholas G. , Sharp Andrew S.P. , Parker Kim H. , Hughes Alun D. , Shore Angela C.
Published: September 2024

Objective:

Hypertension is a recognized risk factor for the development of cognitive impairment and dementia in older adults. Aortic stiffness and altered haemodynamics could promote the transmission of detrimental high pressure pulsatility into the cerebral circulation, potentially damaging brain microvasculature and leading to cognitive impairment. We determined whether reservoir-excess pressure parameters were associated with cognitive function in people with hypertension (HT) and normotension (NT).

Methods:

We studied 35 middle-aged and older treatment-naïve stage II/III HT (office systolic BP 176 ± 17 mmHg) and 35 age-, sex- and body mass index-matched NT (office systolic BP 127 ± 8 mmHg). Parameters derived from reservoir-excess pressure analysis including reservoir pressure integral (INTPR), excess pressure integral (INTXSP), systolic rate constant (SRC), diastolic rate constant (DRC) and pulse wave velocity (PWV) were calculated from an ensemble-averaged aortic pressure waveform derived from radial artery tonometry. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R), Trail Making Test Part A (TMT-A) and Part B (TMT-B).

Results:

All reservoir-excess pressure parameters were greater in HT than NT (all P < 0.05). Greater INTXSP was associated with lower ACE-R score (r
s = −0.31), longer TMT-A (r = 0.31) and TMT-B (r = 0.38). Likewise, greater DRC and PWV were also associated with lower ACE-R score (r
s = −0.27 and r
s = −0.33), longer TMT-A (r = 0.51 and r = 0.40) and TMT-B (r = 0.38 and r = 0.32). Greater INTXSP, DRC and PWV are consistently associated with worse cognitive function in this study.

Conclusions:

These observations support a potential mechanistic link between adverse haemodynamics and a heightened risk of cognitive impairment in older adults with hypertension.
Using an in-office passive leg raise to identify older adults with suboptimal blood pressure control
Authors: Williams Jeremy R. , Cole Molly A. , Pewowaruk Ryan J. , Hein Amy J. , Korcarz Claudia E. , Raza Farhan , Chesler Naomi C. , Eickhoff Jens C. , Gepner Adam D.
Published: September 2024

Introduction:

Passive leg raise (PLR) is a simple, dynamic maneuver that has been used to increase preload to the heart. We hypothesize that PLR may offer a new and efficient office-based tool for assessing blood pressure (BP) control in older adults.

Methods:

One hundred and three veterans (≥60 years old) without known cardiovascular disease and varying degrees of blood pressure control were included in this cross-sectional cohort study. Twenty-four hour ambulatory BP monitoring identified Veterans with optimal and suboptimal BP control (≥125/75 mmHg). Bioimpedance electrodes (Baxter Medical, Deerfield, Illinois, USA) and brachial BP were used to calculate hemodynamic parameter changes across PLR states [pre-PLR, active PLR (3 min), and post-PLR]. Multiple linear regression was used to assess associations between BP control status with changes in hemodynamic parameters between PLR states.

Results:

The 24-h ambulatory BP monitoring identified 43 (42%) older Veterans with optimal BP control (mean age of 70.5 ± 7.0 years) and 55 (54%) with suboptimal BP (mean age of 71.3 ± 8.7 years). Veterans with suboptimal BP control had significantly reduced change in total peripheral resistance (ΔTPR) (7.0 ± 156.0 vs. 127.3 ± 145.6 dynes s/cm5; P = 0.002) following PLR compared with Veterans with optimal BP control. Suboptimal BP control (β = −0.35, P = 0.004) had a significant association with reduced ΔTPR, even after adjusting for demographic variables.

Conclusion:

Measuring PLR-induced hemodynamic changes in the office setting may represent an alternative way to identify older adults with suboptimal BP control when 24-h ambulatory BP monitoring is not available.
Vγ6/Vδ1+ γδ T cells protect from angiotensin II effects on blood pressure and endothelial function in mice
Authors: Mahmoud Ahmad U.M. , Caillon Antoine , Shokoples Brandon , Ferreira Nathanne S. , Comeau Kevin , Hatano Shinya , Yoshikai Yasunobu , Lewis Julia M. , Tigelaar Robert E. , Paradis Pierre , Schiffrin Ernesto L.
Published: September 2024

Objectives:

γδ T cells mediate angiotensin II (AngII)-induced hypertension and vascular injury. γδ T cells expressing specific T-cell receptor (TCR) variable (V) γ chains develop in several waves in the thymus and migrate to specific or diverse tissues. We hypothesized that γδ T cells expressing specific Vγ subtypes in perivascular tissue mediate AngII hypertensive effects.

Methods:

C57BL/6J male mice were infused or not with AngII (490 ng/kg/min, subcutaneously) for 14 days. γδ T-cell Vγ subtypes were profiled by flow cytometry in the spleen, descending thoracic aorta with adherent perivascular adipose tissue (DTAo/PVAT) and mesenteric vessels (MV)/PVAT. Other sets of AngII-infused mice were injected with control or specific anti-Vγ6 or Vγ4 antibodies. Blood pressure (BP) was determined by telemetry, and mesenteric artery function and remodeling by pressurized myography.

Results:

Vγ6/Vδ1+ γδ T cells represented more than 50% of the γδ T-cell Vγ subtypes in DTAo/PVAT and MV/PVAT, whereas Vγ1/2+, Vγ4+ and Vγ6/Vδ1+ γδ T cells were the most abundant Vγ subtypes in the spleen. The frequency of Vγ6/Vδ1+ γδ T cells was increased at least 1.5-fold in the spleen and DTAo/PVAT, and tended to increase in MV/PVAT by AngII. A majority of Vγ6/Vδ1+ γδ T cells were activated in perivascular tissues. Vγ6/Vδ1+ γδ T-cell neutralization caused a steeper BP elevation and greater mesenteric artery endothelial dysfunction in mice infused with AngII. This was associated with more than three-fold increase in activated Vγ6/Vδ1– γδ T cells in perivascular tissues. Depletion of Vγ4+ γδ T cells did not alter AngII detrimental effects.

Conclusion:

Vγ6/Vδ1+ γδ T cells reduce the BP elevation and endothelial dysfunction induced by AngII infusion.
Polydatin accelerates osteoporotic bone repair by inducing the osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells via the PI3K/AKT/GSK-3β/β-catenin pathway
Authors: Zhou Chunhao , Hu Guanyu , Li Yikai , Zheng Sheng
Published: September 2024

Background:

Polydatin (POL), a natural stilbenoid, has multiple pharmacological activities. However, its effect on osteoporotic bone defects has not yet been examined. This study was designed to explore the unknown role of POL on osteoporotic bone repair.

Methods:

The effect of POL on osteogenesis and angiogenesis were investigated firstly. Then a series of angiogenesis-related assays were carried out to explore the relationship between osteogenesis and angiogenesis of POL, and the underlying mechanism was further explored. Whereafter, ovariectomy-induced osteoporosis rats with bone defect were treated with POL or placebo, the imageological and histological examinations were conducted to assess the effect of POL on osteoporotic bone repair.

Results:

The moderate concentrations (1 μM and 10 μM) of POL enhanced the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and elevated the expression of angiogenic-specific markers. Further research found that POL-induced human umbilical vein endothelial cells migration and tube formation through the osteogenesis-angiogenesis coupling of BMSCs, and the POL-induced osteogenesis-angiogenesis coupling was reversed after co-cultured with LY294002. Mechanistically, this was conducted via activating PI3K/AKT/GSK-3β/β-catenin pathway. After that, using the osteoporotic bone defect rat model, the authors, observed that POL facilitated osteoporotic bone repair through enhancing osteogenesis and CD31hiEMCNhi type H-positive vessels formation via the PI3K/AKT/GSK-3β/β-catenin pathway.

Conclusion:

The data above indicated that POL could accelerate osteoporotic bone repair by inducing the osteogenesis-angiogenesis coupling of BMSCs via the PI3K/AKT/GSK-3β/β-catenin pathway, which provided new insight and strategy for osteoporotic bone repair.
Using computed tomography to evaluate anatomic landmarks in Taiwanese trauma patients for insertion of resuscitative endovascular balloon occlusion of the aorta: a retrospective cohort study
Authors: Chien Chih-Ying , Lee Yueh-Lin , Jeng Mei-Jy , Liu Chia-Jen
Published: September 2024

Background:

Hemorrhage, particularly from noncompressible torso hemorrhage (NCTH) in the abdominopelvic region, is a leading cause of preventable trauma deaths. Resuscitative endovascular balloon occlusion of the aorta (REBOA), designed for aortic occlusion, has emerged as a tool for temporary hemorrhage control in recent years. However, attaining optimal REBOA placement in diverse demographic groups, such as Asian populations, may pose challenges owing to unique anatomical and physiological differences.

Materials and methods:

This retrospective study analyzed trauma patients who underwent torso computed tomography (CT) at tertiary hospitals in Taiwan from January 2014 to January 2017. The OsiriX software was used to measure the endovascular lengths in the CT images.

Results:

Among the 223 patients, the median vascular lengths and body measurements were higher in males. The optimal fixed insertion length was identified as 47.5 cm for zone 1 with 99.43% accuracy and 25.5 cm with 82.1% accuracy for zone 3. The landmark-guided method showed 100% accuracy for zone 1 when using the mid-sternum and 94.6% for zone 3 with the umbilicus as the guide with the distance between the umbilicus, xiphoid process, and pubic ramus. External validation confirmed the accuracy of the landmark-guided method.

Conclusions:

For zone 1 occlusions, a range of 44–48 cm insertion length cross-referenced with the mid-sternal landmark is recommended. For zone 3 occlusions, using the umbilicus as a guide with the distance between the umbilicus, xiphoid process, and pubic ramus provided the highest accuracy.
Optimizing Trauma Activation Criteria for a Rural Trauma Center
Authors: Klarr Erin , Rhodes-Lyons Heather Xenia , Symons Rachel
Published: September 2024

BACKGROUND:

There is a need for activation criteria that reflect the different factors affecting rural trauma patients.

OBJECTIVE:

To develop effective activation criteria for a rural trauma center among adults, incorporating variables specific to the geography, mechanisms of injury, and population served.

METHODS:

This is a single-center, retrospective cohort study conducted from (23 years) January 1, 2000, to July 31, 2023. The data collected patient demographics, injury details, morbidity, and preexisting comorbidity. This research included all adult (≥15 years) true Level I trauma activations defined as an injury severity score > 25 and met the need for trauma intervention criteria. The patients were grouped into adult and elderly categories. The analysis utilized a logistic regression model with the outcome of a true Level I trauma activation.

RESULTS:

A total of 19,480 patients were included in the sample; 2,858 (14.6%) met the Level I activation criteria. Elderly Level I activation included assault, pedestrian struck, multiple pelvic fractures, traumatic pneumo/hemothorax, mediastinal fracture, sternum fracture, and flail rib fracture.

CONCLUSION:

Using the findings of the logistic regression model, this center has made more robust activation guidelines adapted to its rural population.
Protective hemodynamics: a novel strategy to manage blood pressure
Authors: D’Amico Filippo , Landoni Giovanni
Published: September 2024

Purpose of review

This editorial aims to highlight the evolving concept of protective hemodynamics in the management of critically ill patients.

Recent findings

Recent literature underscores the limitations of rigid blood pressure targets, particularly in the context of critical care and perioperative management. High blood pressure targets, especially when coupled with high-dose vasopressors, can lead to poor outcomes. ’Protective hemodynamics’ aims to maintain cardiovascular stability while reducing risks associated with interventions.

The implications of adopting protective hemodynamics are profound for both clinical practice and research. Clinically, this approach can reduce iatrogenic harm and improve long-term outcomes for critically ill patients. For research, it opens new avenues for investigating individualized hemodynamic management strategies that prioritize overall patient stability and long-term health over rigid target attainment.
Using National Public Health Accreditation to Explore Quality Improvement and Performance Management in Small Local Health Departments
Authors: Fifolt Matthew , Allen Peg , Crenshaw Andrew , Erwin Paul C. , Lang Britt , Thomas Amy Belflower , Brownson Ross C.
Published: September 2024

Context:

This article focuses on 4 small local health departments (LHDs) that were in the process of seeking Public Health Accreditation Board (PHAB) reaccreditation or Pathways Recognition using PHAB Standards & Measures Version 2022.

Objective:

The objective of this study was to explore the experiences of 4 small LHDs related to Quality Improvement (QI) and Performance Management (PM) in their pursuit of PHAB reaccreditation or Pathways Recognition.

Design:

A team of researchers conducted 22 qualitative interviews with health department leaders and staff. Findings relative to QI/PM represent an embedded case study since they were part of a larger investigation.

Setting:

The research team conducted interviews remotely with health departments located in the West and Midwest.

Participants:

Participants included adults at least 18 years old and employed in 1 of 4 health departments.

Main Outcome Measures:

Emergent themes from this qualitative investigation included using QI/PM tracking systems, building staff buy-in for QI/PM, integrating QI/PM into daily work, and advice for other health departments regarding QI/PM.

Results:

Participants suggested that tracking systems helped them manage QI/PM processes. Staff buy-in for QI/PM was strengthened by building a sense of ownership of the process and connecting improvement processes to outcomes. Health departments integrated QI/PM into daily work by leadership modeling and communicating expectations. Advice for other health departments included finding a QI system that was easy to follow and recognizing the role of QI/PM in improving performance to better support the wellbeing of the community.

Conclusions:

QI/PM are important tools for health department effectiveness. Participants affirmed that the primary purposes of QI/PM are to enhance internal processes and improve community health outcomes. Study findings demonstrate how 4 small health departments integrated QI/PM into their public health practice.
A Quantitative Evaluation of the Effects of Radiation Therapy on the Post-Surgical Breast.
Authors: Becker Miriam , Reese McKay , Yessaillian Andrea , Lopes Kelli , Harfouche Cyril , Leach Garrison , Blair Sarah , Yashar Catheryn , Ojeda-Fournier Haydee , Reid Chris M
Published: September 2024

Background:

Radiation (RT) effects on breast volume may impact breast-conserving therapy (BCT) outcomes, but quantitative information is lacking regarding the extent/timing of volume loss. This study aimed to quantify volume loss by assessing changes in irradiated breasts.

Methods:

Breast volume changes were calculated for 113 patients (115 breasts) following T1 tumor lumpectomies. From preoperative baseline to seven years post-radiation, volumes were calculated from mammograms using π/3* height*radius2. Paired t-tests assessed change over time, with subset analyses of tumor/breast volumes of ≤ 10% (n=67) and > 10% (n=48). Multivariable regression assessed volume change as a function of age, smoking history, diabetes, radiation dosage, fractions, technique, treatment length, boost dose, chemotherapy (hormonal or cytotoxic), baseline breast volume, and time since treatment.

Results:

Patients lost 8.3% of breast volume during surgery. One year following BCT/RT, volume loss was 19.3%. By year five, total volume loss was 26.6%.

Subset analyses demonstrated that in addition to lumpectomy defects, five-year volume loss was 21.7% for tumor/ breast volume > 10% and 29.5 % for tumor/ breast volume ≤ 10%. Volume loss between subgroups was not significantly different (p=0.37). Larger breast volume was a significant predictor of greater volume loss for all five years (p<0.001), followed by diabetes and smoking history.

Conclusion:

Patients with T1 tumors undergoing BCT/RT may lose approximately 20% of breast volume (beyond specimens) within a year, with continued loss for five years. Volume change did not differ significantly according to baseline breast volume, although larger breasts may experience comparatively larger volume changes.
Postoperative Orbital Morphology Observations Following Fronto-Orbital Advancement and Cranial Vault Remodeling in Patients With Unilateral Coronal Synostosis
Authors: Zhang Songchunyuan , Fang Cheng , Lan Dongyi , Wang Yueqing , Dong Chenbin
Published: September 2024

Object:

Observations of preoperative and postoperative orbital morphology following fronto-orbital advancement and cranial vault remodeling (FOA and CVR) in patients with unilateral coronal synostosis (UCS).

Methods:

This retrospective cohort included patients diagnosed with unilateral coronal synostosis and treated with fronto-orbital advancement and cranial vault remodeling at the Children’s Hospital of Fudan University. The orbital height, orbital width, and orbital volume were obtained from head 3-dimensional computed tomography of preoperation and postoperation. The DICOM data of CT were then imported into mimics research version 21.0. The authors measured OH and OW according to the bony landmarks, then reset the parameters of the soft tissue window, and conducted a 3-dimensional reconstruction of the orbital soft tissue to get OV. The preoperative and postoperative measurements of the intact side were compared with the affected side, respectively. Statistical analysis was performed using SPSS version 25.0 (Ρ=0.05).

Results:

Twelve patients with UCS (5 male, 7 female) meeting criteria were included in the study. There were 4 patients with UCS on the left and 8 on the right. The average age at initial surgery was 19.50 months. Before the operation, the data of the intact side and the affected side were compared, respectively, and the difference was found to be significant in OH (Ρ=0.005) and OW (Ρ=0.005), while the OV (Ρ=0.106) was not statistically significant. After procedures of FOA and CVR, the data of the intact side and the affected side were compared, respectively, the significant difference was found in OV (Ρ=0.002), while not in OH (Ρ=0.060) or OW (Ρ=0.066).

Conclusion:

After undergoing the operation of FOA and CVR, the OH and OW of the ipsilateral and contralateral sides of patients with UCS were basically symmetrical, while the volume of the affected orbit was still relatively smaller.
The association among multiple-site chronic pain, sedentary behavior, and major depressive disorders: a mendelian randomization study
Authors: Li Nan-Xi , Chen Cheng-Feng , Zhang Bin
Published: September 2024

Objective

Observational studies have reported that major depressive disorder (MDD) is associated with sedentary behavior (SB) and multiple chronic pain (MCP), but their associations remain unclear. Mendelian randomization analysis was used to assess the association.

Methods

Single nucleotide polymorphisms (SNPs) associated with MCP, SB [time spent watching television (Tel), using a computer (Com), or driving (Dri)], and MDD were collected from genome-wide association studies and screened as instrumental variants with a threshold of 1 × 10−5. Mendelian randomization was performed to examine their associations. Sensitivity analyses were conducted to evaluate robustness.

Results

MCP was associated with a higher risk of MDD [odds ratio (OR) inverse variance weighting (IVW) = 1.88; 95% confidence interval (CI), 1.64–2.15; P = 4.26 × 10−8), and causally related to SB (Tel: ORIVW = 1.23; 95% CI, 1.19–1.26; P = 6.02 × 10−38) (Dri: ORIVW = 1.05; 95% CI, 1.03–1.08; P = 3.92 × 10−5). Causality of SB on MCP was detected for Tel (ORIVW = 1.46; 95% CI, 1.39–1.53; P = 1.40 × 10−54) and Com (ORIVW = 0.88; 95% CI, 0.83–0.93; P = 2.50 × 10−6). No association was observed for SB on MDD. There is currently insufficient evidence to support that leisure activities are a mediating factor in MCP-induced MDD.

Conclusion

There are complex relationships among MCP, SB, and MDD. More research and learning about potential relationships and mechanisms among these phenotypes should be supplied.
Prenatal diagnosis and molecular cytogenetic analyses of a homozygous Robertsonian translocation family with novel mosaic Robertsonian fission karyotype
Authors: Xu Zhen , Luo Huili , Li Manman , OuYang Liu , Xia Zhi
Published: September 2024

Background

Approximately one person in 1000 is a Robertsonian translocation carrier. Errors in the formation of eggs (or more rarely of sperms) may be the cause of Robertsonian translocation. Most Robertsonian translocation carriers are healthy and have a normal lifespan, but do have an increased risk of offsprings with trisomies and pregnancy loss. The fitness of Robertsonian translocation carriers is reduced, but can provide material for evolution.

Materials and methods

We have done prenatal diagnosis and molecular cytogenetic analyses on this homozygous Robertson translocation family. We report a homozygous Robertson translocation family with previously undescribed mosaic Robertsonian fission karyotype.

Results

We identified six Robertsonian translocation carriers in this family. Four were heterozygous translocation carriers of 45,XX or XY,der(14;15)(q10;q10), one was a homozygous translocation carrier of a 44,XY,der(14;15)(q10;q10),der(14;15)(q10;q10), and one was a previously undescribed Robertsonian fission carrier of 45,XN,der(14;15)(q10;q10)[42]/46,XN[58] with normal phenotype.

Conclusion

We reported a previously undescribed mosaic Robertsonian fission karyotype. The homozygosity of Robertsonian translocation for speciation may be a potential mechanism of speciation in humans. In theory, the carriers of homologous Robertsonian translocation cannot produce normal gametes, but Robertson fission made it possible for them to produce normal gametes.
Unmanned aerial vehicles equipped with sensor packages to study spatiotemporal variations of air pollutants in industry parks
Authors: Chen Lang , Pang Xiaobing , Wu Zhentao , Huang Riyang , Hu Junyu , Liu Yi , Zhou Lei , Zhou Jue , Wang Zhiwen
Published: September 2024

Unmanned aerial vehicles (UAVs) equipped with a miniaturized sensor package were developed for aerial observations, which realizes aerial observations affordable to scientists in atmospheric science and achieves aerial measurements in high spatial resolution. UAVs are deployed to a variety of aerial detecting tasks in different scientific scenarios including chemical industry parks (CIPs) with hazardous gases emissions, and some places difficult for humans to reach. In this study, UAV sensing technology was deployed to detect air pollutants in a suburb, a CIP and a natural gas plant, respectively. The effects of atmospheric conditions such as the atmospheric boundary layer height, long-distance transport and atmospheric stability on the spatiotemporal variations of the air pollutants vertical profiles were investigated by the UAV. The UAV with the sensor package was deployed to capture the methane (CH
4
) leakages in a natural gas plant. The spatiotemporal variations of CH
4
in both vertical and horizontal directions studied by UAV were employed to calculate accurate CH
4
emissions, which is crucial to reducing the emissions of greenhouse gases. The low-cost UAV sensing technology for air pollutants was developed by Dr. Xiaobing Pang, who was funded by the Newton Fellowship in 2009 and worked in the University of York.

This article is part of the theme issue ‘Celebrating the 15th anniversary of the Royal Society Newton International Fellowship’.
MYC plus class IIa HDAC inhibition potentiates mitochondrial dysfunction in non-small cell lung cancer
Authors: Park Jina , Chen Ying-Yu , Cao Jennie J. , An Julia , Yen Ray-Whay Chiu , Outen John D. , Baylin Stephen B. , Topper Michael J.
Published: September 2024

MYC is frequently activated in cancer, leading to significant efforts to develop MYC inhibitors. While much progress has been made in targeting MYC, combination treatment strategies are needed to exploit this molecular vulnerability. To this end, we interrogated transcriptome data from cancer cell lines treated with MYC inhibitors and identified HDAC5 and HDAC9, both class IIa HDACs, as therapeutic targets to inhibit concurrently. Notably, these HDAC isoforms, which can be specifically targeted by small molecules, are known augmenters of several hallmarks of cancer. The combination of MYC and class IIa HDAC inhibition induces a significant reduction in viability for NSCLC cell lines with high MYC and mitochondrial pathway activation. Additionally, combination treatment induces a robust reduction of MYC with concomitant elevation of mitochondrial ROS, both of which have a causal relationship with therapeutic efficacy. Confirmation of in vivo efficacy was pursued in several animal model systems, with subsequent molecular correlate derivation confirming the importance of MYC depletion and mitochondrial dysfunction in driving drug efficacy. Ultimately, we define a therapeutic approach combining MYCi and class IIa HDACi to potentiate anti-tumor efficacy in NSCLC.
A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection
Authors: Westfall Susan , Gentile Maria E. , Olsen Tayla M. , Karo-Atar Danielle , Bogza Andrei , Röstel Franziska , Pardy Ryan D. , Mandato Giordano , Fontes Ghislaine , Herbert De’Broski , Melichar Heather J. , Abadie Valerie , Richer Martin J. , Vinh Donald C. , Koenig Joshua F. E. , Harrison Oliver J. , Divangahi Maziar , Weis Sebastian , Gregorieff Alex , King Irah L.
Published: September 2024

Type 1 immunity mediates host defense through pathogen elimination, but whether this pathway also impacts tissue function is unknown. Here we demonstrate that rapid induction of IFNγ signaling coordinates a multi-cellular response that is critical to limit tissue damage and maintain gut motility following infection of mice with a tissue-invasive helminth. IFNγ production is initiated by antigen-independent activation of lamina propria CD8+T cells following MyD88-dependent recognition of the microbiota during helminth-induced barrier invasion. IFNγ acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFNγ sensing also limited the expansion of smooth muscle actin-expressing cells to prevent pathological gut dysmotility. Importantly, this tissue-protective response had limited impact on parasite burden, indicating that IFNγ supports a disease tolerance defense strategy. Our results have important implications for managing the pathophysiological sequelae of post-infectious gut dysfunction and chronic inflammatory diseases associated with stromal remodelling.

HIGHLIGHTS

Type 1 immunity is required for disease tolerance to tissue-invasive infection.

Gut-resident CD8+T cells produce IFNγ in an antigen-independent, yet microbiota-dependent manner.

IFNγ signaling recruits neutrophils in a cell-extrinsic manner to limit helminth-induced tissue injury.

Direct sensing of IFNγ by intestinal stroma is essential to limit tissue damage and maintain gut motility during infection.
TGFβ primes alveolar-like macrophages to induce type I IFN following TLR2 activation
Authors: Thomas Sean M. , Ankley Laurisa M. , Conner Kayla N. , Rapp Alexander W. , McGee Abigail P. , LeSage Francois , Tanner Christopher D. , Vielma Taryn E. , Scheeres Eleanor C. , Obar Joshua J. , Olive Andrew J.
Published: September 2024

Alveolar macrophages (AMs) are key mediators of lung function and are potential targets for therapies during respiratory infections. TGFβ is an important regulator of AM differentiation and maintenance, but how TGFβ directly modulates the innate immune responses of AMs remains unclear. This shortcoming prevents effective targeting of AMs to improve lung function in health and disease. Here we leveraged an optimizedex vivoAM model system, fetal-liver derived alveolar-like macrophages (FLAMs), to dissect the role of TGFβ in AMs. Using transcriptional analysis, we first globally defined how TGFβ regulates gene expression of resting FLAMs. We found that TGFβ maintains the baseline metabolic state of AMs by driving lipid metabolism through oxidative phosphorylation and restricting inflammation. To better understand inflammatory regulation in FLAMs, we next directly tested how TGFβ alters the response to TLR2 agonists. While both TGFβ (+) and TGFβ (−) FLAMs robustly responded to TLR2 agonists, we found an unexpected activation of type I interferon (IFN) responses in FLAMs and primary AMs in a TGFβ-dependent manner. Surprisingly, mitochondrial antiviral signaling protein and the interferon regulator factors 3 and 7 were required for IFN production by TLR2 agonists. Together, these data suggest that TGFβ modulates AM metabolic networks and innate immune signaling cascades to control inflammatory pathways in AMs.
Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation
Authors: Liu Kevin , Titt Uwe , Esplen Nolan , Connell Luke , Konradsson Elise , Yang Ming , Wang Xiaochun , Takaoka Takeshi , Li Ziyi , Koong Albert C. , Mitra Devarati , Mohan Radhe , Loo Billy W. , Lin Steven H. , Schüler Emil
Published: September 2024

Purpose

Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs. spread-out-Bragg-peak [SOBP]) on acute radiation-induced gastrointestinal toxicity (RIGIT) in mice. We also compared RIGIT between synchrotron-based protons and linac-based electrons with matched mean dose rates.

Methods and Materials

We administered abdominal irradiation (12-14 Gy single fraction) to female C57BL/6J mice with an 87 MeV synchrotron-based proton beamline (2 cm diameter field size as a lateral beam). Dose rates were 0.2 Gy/s (S-T pCONV), 0.3 Gy/s (SOBP pCONV), 150 Gy/s (S-T pFLASH), and 230 Gy/s (SOBP pFLASH). RIGIT was assessed by the jejunal regenerating crypt assay and survival. We also compared responses to proton [pFLASH and pCONV] with responses to electron CONV (eCONV, 0.4 Gy/s) and electron FLASH (eFLASH, 188-205 Gy/s).

Results

The number of regenerating jejunal crypts at each matched dose was lowest for pFLASH (similar between S-T and SOBP), greater and similar between pCONV (S-T and SOBP) and eCONV, and greatest for eFLASH. Correspondingly, mice that received pFLASH SOBP had the lowest survival rates (50% at 50 days), followed by pFLASH S-T (80%), and pCONV SOBP (90%), but 100% of mice receiving pCONV S-T survived (log-rankP= 0.047 for the four groups).

Conclusions

Our findings are consistent with an increase in RIGIT after synchrotron-based pFLASH versus pCONV. This negative proton-specific FLASH effect versus linac-based electron irradiation underscores the importance of understanding the physical and biological factors that will allow safe and effective clinical translation.
Dynamic cycles between idea generation and evaluation during creative storytelling
Authors: Liang Xitong , Cai Mingnan , Jing Gaohan , Zhang Chengming , Nichols Emily S , Liu Li
Published: September 2024

Many theories support the notion that creative thinking involves a dynamic transition between idea generation and evaluation, but there is limited evidence of how these two stages interact. The dual process model proposes that spontaneous thinking and deliberate thinking drive these stages and the transitions between them, but there is a debate over whether they operate in parallel or in sequence. To address these gaps, we conducted a functional magnetic resonance imaging (fMRI) study in 41 college students during a creative storytelling task. By analyzing the dynamic brain state, we link the brain states with idea generation and evaluation. The transition patterns between brain states provide evidence for dynamic circulation between idea generation and evaluation during creative storytelling. Using a deep learning approach, we demonstrate an alternating interaction between spontaneous and deliberate thinking, driving the idea generation and evaluation stages and the transitions between them. These findings deepen our understanding of the cognitive and neural mechanisms underlying creative thinking.
MaskMol: Knowledge-guided Molecular Image Pre-Training Framework for Activity Cliffs with Pixel Masking
Authors: Cheng Zhixiang , Xiang Hongxin , Ma Pengsen , Zeng Li , Jin Xin , Yang Xixi , Lin Jianxin , Deng Yang , Song Bosheng , Feng Xinxin , Deng Changhui , Zeng Xiangxiang
Published: September 2024

Activity cliffs, which refer to pairs of molecules that are structurally similar but show significant differences in their potency, can lead to model representation collapse and make the model challenging to distinguish them. Our research indicates that as molecular similarity increases, graph-based methods struggle to capture these nuances, whereas imagebased approaches effectively retain the distinctions. Thus, we developed MaskMol, a knowledge-guided molecular image selfsupervised learning framework. MaskMol accurately learns the representation of molecular images by considering multiple levels of molecular knowledge, such as atoms, bonds, and substructures. By utilizing pixel masking tasks, MaskMol extracts fine-grained information from molecular images, overcoming the limitations of existing deep learning models in identifying subtle structural changes. Experimental results demonstrate MaskMol’s high accuracy and transferability in activity cliff estimation and compound potency prediction across 20 different macromolecular targets, outperforming 25 state-of-the-art deep learning and machine learning approaches. Visualization analyses reveal MaskMol’s high biological interpretability in identifying activity cliff-relevant molecular substructures. Notably, through MaskMol, we identified candidate EP4 inhibitors that could be used to treat tumors. This study not only raises awareness about activity cliffs but also introduces a novel method for molecular image representation learning and virtual screening, advancing drug discovery and providing new insights into structure-activity relationships (SAR). Code is available athttps://github.com/ZhixiangCheng/MaskMol.
Deciphering transcriptional programming during lupin (Lupinus angustifolius) seed development using RNA-seq
Authors: Wainaina Virginia , Rathjen Tina , Hughes Trijntje , Marquardt Annelie , Fletcher Natalie , Casarotto Hayley , McNeil Meredith , McElroy Kerensa , Gao Ling-Ling
Published: September 2024

Lupin (Lupinus spp.)seeds are valued for their high protein content (35-40%) for both human and animal consumption. Seed development in crop plants is a critical factor influencing both seed fate and yield, hence, understanding the molecular mechanisms of seed development is essential. This study conducted a transcriptome analysis of Narrow Leaf Lupin (NLL) during seed development stages (3, 6, 9, 12, 15, 18, and 21 days after flowering) to investigate transcriptional dynamics and identify key candidate genes that control seed development. Approximately 357 million sequencing reads were generated from nine samples from leave, flower and seed tissues, enabling the identification of 34,769 expressed genes. The analysis revealed dynamic gene expression, with early stages marked by high metabolic activity and later stages focusing on storage protein synthesis and nutrient reservoir formation. The differential expression patterns of seed storage protein genes, including cupin groups (α, β, γ, and δ conglutins), were notable. The expression of α and β conglutins increased at later stages (15-21 days after flowering), supporting their role in grain filling and nutrient storage. Genes related to quinolizidine alkaloid biosynthesis, such as lysine/ornithine decarboxylase and purine permease transporter 1, showed late expression patterns suggesting alkaloid synthesis and transport during later stages. Many of the well-established transcription factors (TFs) known for their roles in seed development (bHLH, AP2, MYB, ERF, C2H2, NAC, WRKY, and C3H zinc finger families) showed differential expression, thus reinforcing the validity of our findings. These findings lay the groundwork for understanding the genetic and molecular mechanisms of seed development in lupin, contributing to enhanced crop management and breeding programs.
Supramolecular Enzyme-Peptide Gels for Localized Therapeutic Biocatalysis
Authors: Fuchs Madeline , Seroski Dillon , Morales Bethsymarie Soto , Melgar Lucas , Scibilio Giannia , Ziegler Abigail , Liu Renjie , Keselowsky Benjamin , Hudalla Gregory
Published: September 2024

Enzyme therapeutics are often compromised by poor accumulation within target tissues, necessitating high doses that can exacerbate off-target effects. We report an injectable supramolecular enzyme-peptide gel platform for prolonged local enzyme retentionin vivo. The gel is based on CATCH(+/-) (Co-AssemblingTags based onCHarge-complementarity), cationic and anionic peptide pairs that form β-sheet fibrils upon mixing1. Enzymes recombinantly fused to CATCH(-) peptide integrate into CATCH(+/-) β-sheet fibrils during assembly, resulting in an enzyme-peptide gel. Catalytically-active gels were fabricated with four disparate enzymes: CATCH(-)-NanoLuc luciferase, CATCH(-)-cutinase, CATCH(-)-uricase, and CATCH(-)-adenosine synthase A. CATCH(-)-cutinase gels demonstrated tunability of the platform, while CATCH(-)-NanoLuc gels demonstrated prolonged tissue retention relative to soluble enzyme. CATCH(-)-uricase gels resolved localized inflammation in a gout model, while CATCH(-)-adenosine synthase A gels suppressed localized lipopolysaccharide-induced inflammation. Modular and tunable enzyme content, coupled with prolonged tissue retention, establish CATCH enzyme-peptide gels as a generalizable vehicle for effective local therapeutic biocatalysis.
Photochemical processes drive thermal responses of dissolved organic matter in the dark ocean
Authors: Hu Ang , Cui Yifan , Bercovici Sarah , Tanentzap Andrew J. , Lennon Jay T. , Lin Xiaopei , Yang Yuanhe , Liu Yongqin , Osterholz Helena , Dong Hailiang , Lu Yahai , Jiao Nianzhi , Wang Jianjun
Published: September 2024

How dissolved organic matter (DOM) responds to climate warming is critical for understanding its effectiveness as a natural climate solution. Here, we use a highly resolved dataset of 821 DOM samples covering the surface waters to the deep Atlantic, Southern, and Pacific oceans to examine molecular-level responses to warming water temperatures, i.e. their thermal responses. In general, the strength and diversity of thermal responses among individual molecules both decline towards the deep waters, but they show decreasing and increasing trends with more recalcitrant molecules in concentration, respectively. Their contrasting trends concur with the more important role of photochemical processes in explaining the diversity of thermal responses than the strength. By projecting global ocean thermal responses from 1950-2020, we predict increases in the diversity are unexpectedly largest at deeper depths (> 1,000 m). Such increases could elevate recalcitrant deep-ocean carbon sink by approximately 10 Tg C yr-1which accounts for > 5% of the carbon flux survived to the deep ocean. Our findings highlight the importance of photochemical legacies in driving DOM thermal responses and further help predict the future oceanic carbon sink under global change.
Genomic characterization of plasmids harboringblaNDM-1,-5,-7carbapenemase alleles in clinicalKlebsiella pneumoniaein Pakistan
Authors: Qamar Muhammad Usman , Sierra Roberto , Jabeen Kokab , Rizwan Muhammad , Rashid Ayesha , Dar Yumna Fatima , Andrey Diego O.
Published: September 2024

Klebsiella pneumoniaeis notorious for causing healthcare-associated infections, which become more complicated by the acquisition ofblaNDMgenes via mobile genetic elements. Although Pakistan is a well-established hot spot ofblaNDM-positiveK. pneumoniae, detailed molecular descriptions ofblaNDM-carrying plasmids are scarce. SevenK. pneumoniaeisolates harboringblaNDMwere recovered from clinical sample sources during a six-month period and tested for antimicrobial susceptibility. A long-read approach was used for whole genome sequencing to obtain circularized plasmids and chromosomes for typing, annotation, and comparative analysis. The isolates were susceptible to colistin and tigecycline only among the tested antibiotics. We identified five STs: ST11, ST16, ST716, ST464, and ST2856. Notably, three strains possessed the hypervirulent capsule KL2, while five were classified as O locus type O2a. Evidence of genetic diversity was further highlighted by the presence of four IncC plasmids harboringblaNDM-1, two IncX3 plasmids harboringblaNDM-5, and a single hybrid IncFIB/IncHI1B plasmid harboringblaNDM-7. These plasmids also carried additional ARGs conferring resistance to aminoglycosides, cephalosporins, and fluoroquinolones. We identified the plasmidome of theK. pneumoniaeisolates and characterized the NDM-carrying plasmids. Genetic analysis confirmed the presence ofblaNDM-1andblaNDM-5on broad host range plasmids andblaNDM-7in a previously unreported hybrid plasmid backbone. We emphasized the critical role of plasmids in spreadingblaNDMin the clinical setting in Pakistan. Hence, we stressed the urgent need for enhanced surveillance, not least in LMICs, infection control measures, and adherence to the AWaRe guidelines in antibiotics use.
Allele imbalance in mRNA is selected in tumorigenesis, results from epigenetic alterations and has prognostic relevance
Authors: Palou-Márquez Guillermo , Pericot-Masdevall Pere , Supek Fran
Published: September 2024

Allelic imbalance (AI) in levels of mRNAs that originated from the paternal and maternal copies of a gene can contribute to phenotypic variation and influence disease traits, including cancer. It is widely appreciated that AI at the DNA level, resulting from somatic copy number alterations (CNA) in tumors, generates second-hit events by which tumor suppressor genes are inactivated and oncogenes are activated; the somatic CNAs are also a known cause of AI at the mRNA level. Apart from CNA, other mechanisms could lead to AI in mRNA expression and also drive cancer evolution. By integrating genomic and transcriptomic pan-cancer data, we show that mRNA AI favoring the mutant allele in driver genes is subject to positive selection, generating second-hit events often independently of somatic CNA. The mRNA AI events associate with worse overall survival across all cancer types, outperforming other predictive markers. Various instances of mRNA AI are explained by the epigenetic changes in DNA accessibility and DNA methylation, affecting alleles differently. While we do not rule out that the driver somatic mutations themselves could induce allele-specific expression (we show an example of splicing-altering mutations, selected in various cancer genes), our study suggests that epigenetic alterations commonly act as second-hit events, generating mRNA allelic imbalances that drive cancer and identify new prognostic markers.