bluuebunny/crossref_metadata_2025 huggingface dataset:
HAS THE INITIATION OF A FORMAL PATHWAY FOR TUMOUR TISSUE COLLECTION IN NEURO ONCOLOGY PATIENTS LED TO AN INCREASE IN PATIENT’S HAVING WHOLE GENOME SEQUENCING (WGS), AND HOW WILL THIS IMPACT ONCOLOGY MANAGEMENT IN THE FUTURE?
Authors: Suarez Mr Aeron , Hurwitz Mrs Victoria , Kostick Ms Ellie , Mullens Ms Laura , La Mrs Jessica , Robinson Mrs Charlotte , Hedges Mrs Sarah , Harding Ms Nicola , Sabido Ms Pat , Chia Ms Kazumi , Aliaga-Arias Mr Jahard , Laxton Mr Ross , Eggleton Ms Kelly , Al-Sarraj Prof Safa , Reisz Dr Zita , Bodi Mr Istvan
Published: October 2024

AIMS

To change the standard of care for collection of glial tumour tissue at a London teaching hospital. This would enable WGS on the tumour tissue, and give patients access to further clinical trials.

METHOD

The previous standard of care was for brain tumour pathology samples to be stored in paraﬃn. This was not suitable for WGS or for many clinical trials; the tumour samples needed to be sent to the lab as fresh tissue. The introduction of a genomics clinical nurse specialist meant that relationships were built between the surgical team, pathology teams and ward teams. There was a teaching by one of the neurosurgical team to the theatre staff. Genomics CNS led training for the nursing team. Adults started having WGS in May 2023 but many patient’s still had tissue incorrectly stored and could not have the sequencing performed. There was an introduction of a formal pathway in theatre created by one of the neurosurgeons in Dec 2023.

RESULTS

From May 2023 - November 2023, 58% adult glioma patients had WGS. Since December 2023 - current (March 2023) and the introduction of the formal pathways, 71% had WGS.

CONCLUSION

A formal pathway has now changed the standard of care for collecting tissue. There is still not 100% compliance, and this remains multifactorial. However the introduction of a formal pathway has now increased the percentage of eligible patients receiving WGS. This positive outcome has now led to discussions about freezing the fresh glioma tissue to allow glioma patient’s wider access to clinical trials which they would previously not have had access to.
THE UTILITY OF MULTIPARAMETRIC MRI IN REDUCING DIAGNOSTIC UNCERTAINTY FOR PRIMARY CNS LYMPHOMA
Authors: Goel Ms Aimee , Flintham Mr Robert , Pohl Dr Ute , Wykes Ms Victoria , Sawlani Dr Vijay
Published: October 2024

AIMS

A key limitation in the early treatment initiation in primary central nervous system lymphoma (PCNSL) is the diagnostic delay caused by lack of recognition of a lesion as a possible lymphoma, steroid initiation, and lesion involution, often resulting in inconclusive biopsy. We highlight the importance of multiparametric MRI (MPMRI), which incorporates diffusion weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) and proton magnetic resonance spectroscopy (1H-MRS) in addition to standard MRI sequences in resolving diagnostic uncertainty for PCNSL.

METHOD

We present a consecutive series of 10 patients at our centre with histology-proven PCNSL (speciﬁcally, diffuse large B-cell lymphoma of the CNS) who underwent multiparametric MRI. We retrospectively analyse the qualitative and semi-quantitative parameters and assess their radiological concordance for this diagnosis.

RESULTS

We note overall low apparent diffusion coeﬃcient on DWI (mean ADCmin of 0.74), high percentage signal recovery on perfusion weighted imaging (mean 170%), a high choline-creatine ratio and a high-grade lipid peak on MRS giving a “twin-tower” appearance. Nine of ten patients had MRMRI ﬁndings concordant for PCNSL, deﬁned as at least 3 of 4 parameters being consistent for PCNSL.

CONCLUSION

We propose that concordance between these imaging multiparametric modalities could be used as a radiological predictor of PCNSL, reducing diagnostic delays, providing a more accurate biopsy target, and resulting in quicker treatment initiation.
UNDERSTANDING THE MANAGEMENT OF MALIGNANT GLIOMAS DURING COVID-19 PANDEMIC IN A HIGH VOLUME TERTIARY GOVERNMENT HOSPITAL IN THE PHILIPPINES
Authors: Gatdula Dr Francis James
Published: October 2024

AIMS

Malignant glioma is a common primary brain tumor with a great burden of disease. When COVID-19 set in, it became a challenge to manage an already diﬃcult treatment process in low-resource-setting centers. Despite this, conventional recommendations and standard treatment protocols are followed. However, outcomes were perceived to deviate from the convention, hence the reason for this study which is to understand the nature of outcomes in the management of malignant gliomas during the COVID-19 pandemic in Southern Philippines Medical Center (SPMC), the largest government tertiary hospital in the Philippines.

METHOD

A retrospective chart review of nine clinically and histologically diagnosed cases of malignant gliomas admitted in SPMC between April 2020 to September 2021 was performed. The clinical presentations, image correlation, and outcomes were listed. Then, classiﬁed as desirable, undesirable but acceptable, or unacceptable based on factors identiﬁed. Qualitative analysis by deduction including outcomes determining possible modiﬁcations in treatment of future cases was done.

RESULTS

Of the nine cases, one was listed as desirable, one with unacceptable outcome due to management complications, and the rest were labeled as undesirable but acceptable either because of advanced disease or poor KPS score. Three major factors were determined: the roles of pre-hospital and initial treatment delays, the decision for surgical treatment, and the COVID-19 pandemic.

CONCLUSION

The shift in the outcomes of malignant gliomas during COVID-19 shows the management challenge in low resource centers. There is an increase in highly malignant cases with guarded prognosis due to lack of education, support, and resources in terms of early diagnosis, treatment, and post-surgical care. This was aggravated by the restrictions imposed by the pandemic and ﬁnancial crisis, especially for patients below the poverty line. Delays in management show a signiﬁcant inﬂuence on prognosis regardless of treatment. As such, possible modiﬁcations in the current treatment algorithm are hereby recommended.
MULTI-AGENCY DEVELOPMENT OF A NEW INFORMATION RESOURCE FOR PATIENTS WITH BRAIN METASTASES
Authors: Watson Ms Rhona , Austin Ms Gemma , Bulbeck Dr Helen
Published: October 2024

AIMS

Based in a large neuro-oncology centre which provides specialist care for hundreds of patients with BM per year, the authors identiﬁed a need for relevant, non-disease speciﬁc, technically accurate and holistically focussed patient information material. This project aimed to develop a comprehensive and patient-focussed information resource for patients with BM.

METHOD

A scoping exercise of twenty UK-based cancer charity websites was carried out. Generic cancer charity sites and sites of charities supporting the four main primary cancer groups which metastasize to the brain were targeted. Information pertaining to BM was collated and reviewed by a multidisciplinary group to assess for scope and quality of information provided. Particular attention was paid to identifying information which was technically accurate and speciﬁcally addressed the holistic needs of this patient group.

RESULTS

Information found was primary disease-speciﬁc, technically inaccurate and did not acknowledge the holistic needs of the patient. This exercise highlighted the need for comprehensive and relevant patient-focussed information material. A working group consisting of health professionals and BrainsTrust charity staff was formed to create an effective patient information resource. Existing BrainsTrust information templates were used to structure the new resource. Evidence-based clinical information was provided by the healthcare professionals involved and holistic information was created collaboratively with charity input. A patient reviewer was enlisted to provide feedback on draft versions.

CONCLUSION

This project resulted in production of a patient-focussed and comprehensive information resource on BM. Patient and healthcare professional feedback to date has been positive.
The HAT1 transcription factor regulates photomorphogenesis and skotomorphogenesis via phytohormone levels
Authors: Zhao Yuqing , Han Qing , Kang Xinke , Tan Wenrong , Yao Xiuhong , Zhang Yang , Shi Haoyu , Xia Ran , Wu Xuemei , Lin Honghui , Zhang Dawei
Published: October 2024

Plants dynamically modulate their growth and development to acclimate to the fluctuating light environment via a complex phytohormone network. However, the dynamic molecular regulatory mechanisms underlying how plants regulate phytohormones during skotomorphogenesis and photomorphogenesis are largely unknown. Here, we identified a HD-ZIP II transcription factor, HOMEODOMAIN ARABIDOPSIS THALIANA1 (HAT1), as a key node that modulates the dose effects of brassinosteroids (BRs) and auxin on hypocotyl growth during skotomorphogenesis and photomorphogenesis. Compared with the wild-type (Col-0), both HAT1 loss of function and its overexpression led to disrupted photomorphogenic and skotomorphogenic hypocotyl growth. HAT1 overexpression (HAT1OX) plants displayed longer hypocotyls in the light but shorter hypocotyls in darkness, whereas the triple mutant hat1hat2hat3 showed the opposite phenotype. Furthermore, we found that CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) interacted with dephosphorylated HAT1 and facilitated the degradation of HAT1 by ubiquitination in darkness, while HAT1 was phosphorylated and stabilized by BRASSINOSTEROID INSENSITIVE2 (BIN2) in the light. Interestingly, we observed distinct dose-dependent effects of BR and auxin on hypocotyl elongation under varying light conditions and that HAT1 functioned as a key node in this process. The shorter hypocotyl of HAT1OX in darkness was due to the inhibition of BR biosynthetic gene BRASSINOSTEROID-6-OXIDASE2 (BR6OX2) expression to reduce BRs content, while brassinolide (BL) treatment alleviated this growth repression. In the light, HAT1 inhibited BR biosynthesis but enhanced auxin signaling by directly repressing IAA3/SHORT HYPOCOTYL 2 (SHY2) expression. Our findings uncover a dual function of HAT1 in regulating BR biosynthesis and auxin signaling that is crucial for ensuring proper skotomorphogenic and photomorphogenic growth.
NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2-mediated osteoblast differentiation
Authors: Geng Ying , Bao Chen , Chen Yue , Yan Ziwei , Miao Fen , Wang Ting , Li Yingyi , Li Lu , Sun Wen , Xu Yan
Published: October 2024

Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied pattern-recognition receptors, and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that the SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contributes to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation.
Epidemiology and management of congenital anomalies in neonates in a hospital in Northern India
Authors: Verma Akanksha , Verma Manoj K , Priyanka Vallepu L , Naranje Kirti , Singh Anita , Roy Abhijeet , Paul Abhishek , Phadke Shubha , Kumar Basant
Published: October 2024

Recent evidence shows a shift in neonatal mortality causes, with an increasing proportion due to birth defects. This study aimed to determine the prevalence and treatment outcomes of congenital anomalies (CAs) at a tertiary referral center in Northern India. This retrospective observational study was conducted over 7 years (May 2014–December 2021) and included all inborn and outborn neonates admitted with a diagnosis of CA as per ICD-10 classification in a level 3 NICU in North India. The prevalence of CAs was 8.9% (332 out of 3734 neonates). The most commonly affected systems were cardiovascular (33.4%), gastrointestinal (19.8%), and genitourinary (19.8%). While 57.5% of these defects could potentially be addressed through pediatric and cardiovascular surgery, only a small proportion of eligible neonates received timely surgical intervention due to delayed referrals and financial constraints. The mortality rate was 16.8%. This study highlights the significant burden of CAs in Northern India, emphasizing the need for enhanced capacity building, better facilities, and increased awareness for timely referrals. The findings underscore the importance of multidisciplinary collaborations and upgraded healthcare services to inspire further research and preventive strategies to mitigate birth defects. Given the context of a low- and middle-income country, this study’s insights into the prevalence, challenges, and outcomes of CAs are particularly relevant, highlighting the necessity of accessible and affordable healthcare solutions in such settings.
Assessing the potential of native copepods in Guatemala for Aedes vector control
Authors: Dambach Peter , Louis Valérie R , Duarte Silvia , Monzón Vivian , García-Gallardo Edgar Orlando , Reyes-Ramirez Miguel Angel , Felipe-Díaz Juan Pablo , Montenegro-Quiñonez Carlos Alberto
Published: October 2024

Background

In this study we examine the feeding efficiency of copepods locally found in Guatemala on first instar Aedes aegypti larvae. Copepods are a potential tool for Aedes vector control that has shown promising results in the laboratory and in community-based field trials.

Methods

Four different copepod species from different habitat types were included in the laboratory assays of this study.

Results

All four tested copepod species decreased the number of the first instar Aedes larvae that were inserted into the glass vessels compared with controls. However, average predation rates between the tested species were highly different, with Thermocyclops crassus and Mesocyclops longisetus achieving the highest, with 31.0% (standard deviation [SD] 18.9) and 28. 9% (SD 11.2), respectively.

Conclusions

The copepod species with identified high predation rates are potential candidates for planned and other future field trials for community-based Aedes vector control with copepods in the region.
The Predictability of Clinical Findings and Radiographs for Detecting Tarsal Coalition
Authors: Nunally Kianna D , Pigeolet Manon , Miller Patricia E , Shea Jodie E , May Collin , Shore Benjamin J
Published: October 2024

Introduction:

Tarsal coalition is a disorder of the foot characterized by the abnormal union between 2 or more of the tarsal bones. A minority of patients will develop pain and limited motion when reaching adolescence, for whom surgical resection of the coalition may be necessary. The diagnostic value of clinical and radiologic signs remains unclear. The aim of this study is to assess the predictive value of clinical symptoms and plain x-rays to diagnose tarsal coalition in symptomatic patients.

Methods:

We performed a retrospective chart review of patients with clinical suspicion of tarsal coalition between January 2011 and November 2019. Patient demographic data; clinical data on pain, limited motion, peroneal spasm, recurrent, or previous trauma; and radiologic data on the presence and type of coalition were collected. Multivariable general estimating equations analysis was used to assess associations between demographic and clinical characteristics and the likelihood of a positive coalition diagnosis.

Results:

The study cohort was 336 patients (672 feet) with a mean age of 13 years and a 1:1 sex distribution. Thirt-eight percent of feet were diagnosed with a coalition of which 53% were talocalcaneal and 41% were calcaneonavicular. Coalitions were significantly more common in younger patients, males (OR 1.66, P=0.04), patients with lower BMI (OR 0.96, P=0.045), and patients who presented with painful feet (OR 1.59, P=0.04) or feet with limited motion (OR 7.49, P<0.001). Diagnostic utility of plain x-ray compared with CT diagnosis yielded a sensitivity of 76% and a specificity of 94%, with higher sensitivity (90%) in calcaneonavicular coalitions than in talocalcaneal (66%).

Discussion:

Our study shows that limited subtalar movement, male sex, and low BMI have a high predictive value for tarsal coalition in symptomatic patients. Classic clinical findings that were not predictive of coalition in our cohort of symptomatic patients included peroneal spasm, recurrent ankle sprains, and recent trauma. Plain x-rays offer a reliable alternative to CT for diagnosis, especially for calcaneonavicular coalitions.

Level of Evidence:

Level III—retrospective comparative study
Cancer therapy-related interstitial lung disease
Authors: Zhou Chengzhi , Deng Haiyi , Yang Yilin , Wang Fei , Lin Xinqing , Liu Ming , Xie Xiaohong , Luan Tao , Zhong Nanshan
Published: October 2024

With the increasing utilization of cancer therapy, the incidence of lung injury associated with these treatments continues to rise. The recognition of pulmonary toxicity related to cancer therapy has become increasingly critical, for which interstitial lung disease (ILD) is a common cause of mortality. Cancer therapy-related ILD (CT-ILD) can result from a variety of treatments including chemotherapy, targeted therapy, immune checkpoint inhibitors, antibody–drug conjugates, and radiotherapy. CT-ILD may progress rapidly and even be life-threatening; therefore, prompt diagnosis and timely treatment are crucial for effective management. This review aims to provide valuable information on the risk factors associated with CT-ILD; elucidate its underlying mechanisms; discuss its clinical features, imaging, and histological manifestations; and emphasize the clinical-related views of its diagnosis. In addition, this review provides an overview of grading, typing, and staging treatment strategies used for the management of CT-ILD.
Intrafocal Pinning in Distal Extraarticular Radius Fracture: A Retrospective Study Based on Patient Age
Authors: Asiry Abdulaziz , De Villeneuve Bargemon Jean Baptiste , Delclaux Stéphanie , Mansat Pierre , Gandolfi Silvia , Lupon Elise
Published: October 2024

Background:

Percutaneous intrafocal pinning is one of the many surgical options for extraarticular distal radius fracture with minimal comminution. This study aims to describe the role and indications of intrafocal pinning.

Methods:

This monocentric, retrospective study included 49 patients who underwent intrafocal pinning for distal radius fractures in 2013 in our French hand surgery department. All the patients underwent posteroanterior and lateral x-ray on days 2 and 45 to measure radial inclination, distal radioulnar index, and volar tilt.

Results:

The mean age of the patients was 45.4 years, with women representing approximately 61.2% of the sample (n = 30). The patients were divided into three groups: group A (17–50 y), 26 patients; group B (50–70 y), 15 patients; and group C (>70 y), eight patients. We documented on x-ray images, 21 secondary displacements, including seven in group C. There were three displacements (all in group C) and one surgical revision within 15 days for a previous displacement. The distal radioulnar index increased in all three groups.

Conclusions:

The percutaneous intrafocal pinning fixation technique exposes a high risk of complications, especially for those older than 50 years, for whom this technique should be avoided. Overall, due to the frequency of secondary displacements encountered, our first-line treatment favors plate osteosynthesis for all patients. Pinning fixation should only be considered with caution in younger patients if plate osteosynthesis is not possible, but it requires a strict 6-week immobilization. The fracture morphology must also be considered.
Is My Doctor Human? Acceptance of AI among Patients with Breast Cancer
Authors: Kenig Nitzan , Muntaner Vives Aina , Monton Echeverria Javier
Published: October 2024

Artificial intelligence (AI) is becoming increasingly important in society, and medicine can benefit from its advantages. What scenario can we envision when AI becomes as powerful and accurate as human physicians? How will the traditional patient–doctor relationship be affected by AI? Will patients come to trust and accept AI-assisted healthcare as much as their human counterparts? Our research team has been working on applications of AI in plastic surgery for more than 4 years. Between 2020 and 2024, AI algorithms were developed by the authors and applied on patients for symmetry evaluation after breast cancer surgery. Patients were aware of being evaluated with images for AI model training and assessment. Feedback was reported, and a survey was carried out among patients who underwent evaluation by our team. Among patients with breast cancer who underwent surgical reconstruction, 65% of patients reported very high levels of comfort with AI, given that it was mediated by a human doctor. Patients stated that nondoctor-mediated AI in medicine would greatly reduce trust. The influence of AI on the patient–doctor relationship is an important aspect that will greatly affect medicine. In this preliminary work, patients showed high levels of trust and comfort with the use of AI in healthcare, despite stating that they knew little about AI. Patients insisted that the mediation of a human doctor is key for acceptance. Currently, little is known about the acceptance of AI in medical roles among patients.
Lymphocytic Esophagitis
Authors: El Halabi Maan , Saoud Carla , Nasser Selim M.
Published: October 2024

Background:

Lymphocytic esophagitis (LyE) is a rare condition that has been reported in several case studies, but its diagnostic criteria and clinical significance are inconsistent. There are no established clinical associations, except for Crohn’s disease in children. Our study aimed to determine if patients with LyE have distinct demographic or clinical characteristics when compared with patients with increased intraepithelial lymphocytes (IEL) in their esophageal biopsy.

Methods:

We conducted a retrospective review of all esophageal biopsies between 2008 and 2023 in 2 medical centers. After excluding cases that met criteria for specific disorders, we identified all cases with increased IEL and compared their clinical, demographic, and endoscopic characteristics to those of LyE.

Results:

We identified 381 cases with increased IEL, of which 15 met the criteria for LyE. Patients diagnosed with LyE showed no distinctive demographic, endoscopic, or associated morbidities. The gradual increase in esophageal IEL was not associated with any differences in demographic, endoscopic, or clinicopathologic findings.

Conclusion:

Our findings suggest that lymphocytic esophagitis is not a well-defined clinicopathologic entity but rather a rare and nonspecific histologic pattern associated with various esophageal disorders. Further studies should aim to differentiate between the underlying causes of this histologic pattern, rather than defining it as a single clinicopathologic entity.
Outcomes of Hydroxyapatite Bone Cement for Craniofacial Reconstruction in 1983 Patients
Authors: Elemosho Abdulaziz , Kluemper Jude C. , Pfahl Emily , Mitchell Kerry-Ann S.
Published: October 2024

Background:

Hydroxyapatite bone cement (HABC) has evolved to have diverse applications in craniofacial reconstruction. This ranges from filling cranial defects to secondary contouring of residual defects after primary surgeries. This study aims to determine patient outcomes after reconstruction with HABCs.

Methods:

A systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. PubMed, Embase, Web of Science, and Cochrane Library databases were queried. The results were limited to English-language literature with extractable data on HABC for craniofacial reconstruction.

Results:

A total of 1983 patients were included in the final analysis from 35 studies. HABCs were mostly used for large defect cranioplasty (21.5%), retrosigmoid (44.6%) and translabyrinthine cranioplasty (8.9%), and correction of residual craniofacial defects after congenital craniofacial surgeries (25%). The rates of cerebrospinal fluid (CSF) leak and infection/explantation were 0% and 7.5% [95% CI: 2.4–11.8] for large defect cranioplasty and 0.8% [0.03–2.07] and 1.5% [95% CI: 0.92–3.3] for retrosigmoid cranioplasty, respectively. The infection/explantation rate was 6.2% [95% CI: 2.6–18.7] for HABCs in the correction of residual craniofacial defects after congenital craniofacial surgeries. The total reoperation rates were 20.4% % [95% CI: 4.8–11.8] for large defect cranioplasty and 12% [95% CI: 3.3–15.3] for correction of residual defects after congenital craniofacial surgeries. Aesthetic satisfaction rates were 93.1% [95% CI: 90.3–98.8] for large defect cranioplasty, 99.4% [95% CI 97.2–99.9] for retrosigmoid cranioplasty, and 92.6% [95% CI: 83.3–95.8] for HABC use in the correction of residual craniofacial defects after congenital craniofacial surgeries.

Conclusion:

HABC is versatile and associated with a high level of patient reported aesthetic satisfaction after cranioplasty and may have a comparably lower complication profile than those of most other alloplastic materials.
Efficacy of Molding Helmet Therapy following Suturectomy for Craniosynostosis: A Single-center, Retrospective Analysis in Japan
Authors: Kurimoto Michihiro , Nawashiro Tomoki , Nagakura Masamune , Kato Mihoko
Published: October 2024

Craniosynostosis limits normal cranial growth, significantly affecting the growth and development of children. This increase in intracranial pressure results in significant cosmetic and functional losses. This study investigated the efficacy of combining molding helmets with suturectomy for craniosynostosis. Patients who underwent suturectomy and molding helmet therapy for craniosynostosis at a single institution between 2017 and 2024 were included. Changes in cephalic index (CI) and cranial vault asymmetry index (CVAI) were analyzed. A total of 14 patients (12 males, 2 females) were included, with a median age of 4.5 months (2–6 mo). The affected sutures were as follows: sagittal (n=8), bilateral coronal (n=4), unilateral coronal (n=1), and lambdoid (n=1) sutures. The median duration of postoperative molding helmet therapy was 44.5 weeks. For the sagittal suture group, the median preoperative CI, median postoperative CI, and rate of change were 72.0 (68.3–85.8), 77.0 (72.1–86.4), and 0.0646, respectively. For the bilateral coronal suture group, measurements for the same parameters were 104.0 (99.3–110.0), 92.5 (89.1–94.5), and 0.1114, respectively. For the unilateral coronal group, the measured parameters were 89.0 (87.7–91.2), 84.0 (81.2–87.1), and 0.059, respectively. Although all suture types showed improvement in cranial shape, with sagittal synostosis showing the most significant change, our findings did not support the added benefit of molding helmet therapy. Overall, the study suggests that suturectomy is a crucial first step in craniosynostosis treatment, leading to improvements in cranial morphology and growth.
Angiotensin II for Catecholamine Resistant Vasodilatory Shock in Patients with Acute Kidney Injury: A Post-Hoc Analysis of the ATHOS-3 Trial
Authors: Chaba Anis , Zarbock Alexander , Forni Lui G. , Hästbacka Johanna , Korneva Elena , Landoni Giovanni , Pickkers Peter , Bellomo Rinaldo
Published: October 2024

Objective

The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear.

Methods

We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) -3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe.

We included patients with all stages AKI at initiation of ANG II or placebo and assessed 28-day mortality as primary outcome. We studied mean arterial pressure (MAP) response and days alive and free from renal replacement therapy (RRT) up to day seven as secondary outcome.

Results

Of 321 ATHOS-3 patients, 203 (63%) had AKI at randomization, with stage 3 AKI being dominant (67%). Median age was 63 years and median APACHE II score was 30. By day 28, overall, 118 (58%) of patients had died (53% with ANGII vs. 63% with placebo, HR = 0.75, 95% CI [0.52-1.08], p = 0.121). Among AKI stage 3 patients, however, ANGII was associated with significantly lower mortality (48% vs. 67%, HR = 0.57, 95% CI [0.36-0.91], p = 0.024). Additionally, in this subgroup, compared with placebo, patients receiving ANGII were more likely to achieve a MAP response (p < 0.001) and had more days alive and free from RRT (p < 0.001).

Conclusions

Compared with placebo, in patients with catecholamine-resistant vasodilatory shock and stage 3 AKI, ANGII is associated with lower 28-day, greater likelihood of MAP response, and more days alive and free from RRT. These findings support the conduct of future ANGII trials in patients with stage 3 AKI.
Differentially expressed lncRNAs in SOD1
G93A
mice skeletal muscle: H19, Myhas and Neat1 as potential biomarkers in amyotrophic lateral sclerosis
Authors: López-Royo Tresa , Moreno-Martínez Laura , Zaragoza Pilar , García-Redondo Alberto , Manzano Raquel , Osta Rosario
Published: October 2024

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor function and muscle mass loss. Despite extensive research in the field, the underlying causes of ALS remain incompletely understood, contributing to the absence of specific diagnostic and prognostic biomarkers and effective therapies. This study investigates the expression of long-non-coding RNAs (lncRNAs) in skeletal muscle as a potential source of biomarkers and therapeutic targets for the disease. The expression profiles of 12 lncRNAs, selected from the literature, were evaluated across different disease stages in tissue and muscle biopsies from the SOD1
G93A
transgenic mouse model of ALS. Nine out of the 12 lncRNAs were differentially expressed, with Pvt1, H19 and Neat1 showing notable increases in the symptomatic stages of the disease, and suggesting their potential as candidate biomarkers to support diagnosis and key players in muscle pathophysiology in ALS. Furthermore, the progression of Myhas and H19 RNA levels across disease stages correlated with longevity in the SOD1
G93A
animal model, effectively discriminating between long- and short-term survival individuals, thereby highlighting their potential as prognostic indicators. These findings underscore the involvement of lncRNAs, especially H19 and Myhas, in ALS pathophysiology, offering novel insights for diagnostic, prognostic and therapeutic targets.
Clinical performance of proenkephalin A 119-159 for the early diagnosis of acute kidney injury in patients with sepsis or septic shock
Authors: Schulte Janin , Dépret François , Hartmann Oliver , Pickkers Peter , Laterre Pierre-François , Uhle Florian ,   AdrenOSS-1 study investigators
Published: October 2024

Background

Sepsis-associated acute kidney injury (AKI) is a severe condition associated with unfavorable outcomes in critically ill patients, not least because of its delayed diagnosis and management due to limitations in the current standard of care. We aimed to evaluate the performance of sphingotest® penKid® for the early diagnosis of AKI in patients with sepsis or septic shock.

Methods

Plasma proenkephalin A 119–159 (penKid) was measured in 120 healthy subjects and 529 critically ill sepsis patients. Subgroup analyses were performed for patients with and without a history of heart failure or hypertension. The clinical performance for the diagnosis of AKI within 48 hours (AKI48h) was calculated using the upper limit of the penKid reference range. To improve clinical decision-making, interpretation bands and likelihood ratios for optimized rule-in and rule-out performance were established.

Results

Of the 529 patients with sepsis or septic shock, 328 were male (62%), and the median age was 66 (interquartile range 56–75) years. Two hundred thirty-four (44%) patients were diagnosed with AKI48h, and those patients presented increased penKid levels on intensive care unit admission compared with patients without AKI48h, with an area under the curve of 0.87 (95% confidence interval [CI] 0.84–0.90, p<0.0001). A penKid cut-off of 89 pmol/L, corresponding to the 97.5thpercentile in the healthy reference population, resulted in 72% sensitivity (95% CI 66–77%), 83% specificity (95% CI 78–87%), 77% positive predictive value (95% CI 71–82%), 79% negative predictive value (95% CI 74–83%), a positive likelihood ratio of 4.2, and a negative likelihood ratio of 0.34 to diagnose AKI48h. An improved performance was obtained when patients with a history of chronic heart failure and/or hypertension were excluded. PenKid cutoff values of 54 pmol/L (>92% sensitivity) and 105 pmol/L (>92% specificity) were derived to establish actionable interpretation bands for diagnostic rule-in and rule-out.

Conclusions

The sphingotest® penKid® assay can facilitate an early diagnosis of AKI up to 48 hours before the KDIGO criteria are met. Based on the present results, the assay was registered as an aid in the early diagnosis of AKI in patients with sepsis or septic shock.
The further development of cold plasma technology: The effectiveness of a contactless, indirect atmospheric cold plasma method for germ reduction on surfaces in vitro and in vivo
Authors: Schmelz Ulrich , Schaal Tom , Hämmerle Gilbert , Tischendorf Tim
Published: October 2024

This study investigates the antimicrobial potential of an indirect cold plasma method for the treatment of wounds. Indirect plasma methods differ from direct methods in that the cold plasma does not come into direct contact with the surface to be treated. The indirect plasma method described here has been implemented in the PLASMOHEAL device. The device generates an aerosol of liquid particles, which is conditioned with plasma reaction products and passed over the areas to be treated without contact. In vitro tests show a significant germ reduction of 3.4 to 4.5 log levels against various microorganisms. In vivo tests on volunteers demonstrate a reduction in E. coli contamination of 4.06 to 5.15 log levels. These results show that indirect plasma methods can achieve equivalent effects to direct methods. The highly effective, pain-free treatment at moderate costs make the indirect plasma method a promising option in modern wound care.
Polygenic risk score analysis suggests hypothyroidism as a risk factor for Alzheimer’s disease
Authors: Piras Ignazio S. , Naymik Marcus A. , Don Janith , Schork Nicholas J. , Saner Don , Huentelman Matthew J.
Published: October 2024

Utilizing the All of Us cohort, this study explores the relationship between clinical conditions, and AD risk, shedding light on potential preventative measures. We selected a subset of non-AD affected individuals aged 60 and older (n = 72,044). Polygenic Risk Scores (PRS) were calculated to assess AD risk, which were then associated with medical conditions. A replication study was conducted in the UK Biobank to validate the findings. We found significant association between AD-PRS and nine conditions, with the most significant being hypothyroidism (adj-p < 1.3-06). The AD-PRS was significantly lower in participants with hypothyroidism, and was further confirmed in a replication study using the UK Biobank data (n=390,543; p= 1.3-23). Our results demonstrate that the absence of hypothyroidism might be a factor enhancing AD resilience since it can balance the genetic risk factors, as non-affected individuals exhibited a significantly higher AD-PRS than individuals with hypothyroidism.
nsGSLs on tumors impair anti-tumor immune responses by OT-I T cellsin vitroand support tumor growthin vivo
Authors: Verkerk Tamara , Selten Aimée A.F. , Zandhuis Nordin D. , Zhang Tao , Wuhrer Manfred , Spaapen Robbert M. , van Ham S. Marieke
Published: October 2024

Tumors often evolve to engage numerous strategies to circumvent detection by the immune system. Our group recently discovered elevated neolacto-series glycosphingolipids (nsGSL) surface levels as a possible immune evasion mechanism of tumors. We demonstrated a direct disruption of both innate and adaptive anti-tumor immunityin vitrowhen expression of nsGSLs was upregulated on established target cells. It remains unclear however, whetherin vivonsGSLs play an active role in tumor development and can aid tumors in evading immune responses.

To investigate whether nsGSLs facilitate tumor progressionin vivo, we first established a murine model system using MC38-OVA cell lines with varying cell surface levels of nsGSLs.In vitroanalysis revealed reduced MHC-I accessibility on tumor cells with elevated nsGSLs profiles, leading to diminished activation of OVA-specific OT-I T cells as evidenced by decreased expression of CD25, CD69, and production of IFNγ, which subsequently resulted in decreased tumor cell death. Subsequentin vivoexperiments investigating tumor outgrowth after engraftment of subcutaneously injected MC38-OVA cell lines with low or high cell surface levels of nsGSLs demonstrated better growth of nsGSL-rich tumor cells compared to nsGSL-poor tumors which could be controlled. Together these results suggest that nsGSLs expressed by tumors can facilitate immune evasion and subsequent tumor progression. These data pave the way to explore whether targeting of the GSL pathway with specific inhibitors could be advantageous as a therapy against tumors with high nsGSL levels.
Dental biofilms contain DNase I-resistant Z-DNA and G-quadruplexes
Authors: Evans Dominique C. S. , Kristensen Mathilde F. , Palmén Lorena G. , Knap Inge , Tiwari Manish K. , Schlafer Sebastian , Meyer Rikke L.
Published: October 2024

eDNA is a major component of the extracellular matrix of bacterial biofilms, and recent studies have shown that biofilms from many pathogens contain both Z-DNA and G-quadruplex (G4) structures in addition to the canonical B-DNA double helix. These secondary DNA structures provide new emergent functions to the biofilm, most notably by making biofilms more resilient by protecting them from nucleases. In dental biofilms, it is largely unknown what conformation eDNA adopts, and the aim of this study was to determine if dental biofilms contain non-canonical secondary DNA structures.

In this study, we visualised B-DNA, G4, and Z-DNA in dental biofilms from 10 healthy subjects and from 10 caries-active subjects using fluorescence immunolabeling and confocal microscopy. eDNA formed large structures surrounding clusters of microorganisms that contained B-DNA, G4, and Z-DNA in the majority of the samples. We also identified microorganisms outside of these large eDNA structures that contained smaller G4 and Z-DNA structures associated to cell surfaces. G4 and Z-DNA are resistant to degradation by the commonly used mammalian DNase I. We verified this resistance in dental biofilms, and we suggest that these structures present a novel target for improved enzyme formulations for controlling oral biofilms and, more broadly, any biofilm that contains G4 and Z-DNA.
The emergence of Fluoroquinolone resistant and Extended-spectrum beta-lactamase-producingSalmonella spp.isolated from Poultry in Pakistan
Authors: Irfan Rimsha , Uzair Bushra , Khan Eid Nawaz , Saeed Abdullah
Published: October 2024

The rise of antimicrobial-resistant and Extended Spectrum Beta Lactamases producingSalmonellastrains in poultry is a severe health threat worldwide, particularly in developing countries like Pakistan. The current study aimed to investigate the isolation and identification of Cefotaxime and Ciprofloxacin-ResistantSalmonellastrains originating from poultry. During this study, 78 (26.0%)Salmonellastrains were isolated from 300 diverse poultry samples. The isolated 78Salmonellastrains were identified asS. pullorum,S. gallinarum,S. enteritidis,S. enterica,S. paratyphi,S. typhimurium,S. typhi,S. arizonae,and 19% otherSalmonella spp. by API 20E method. The antibiotic susceptibility profile showed that 61% of MDRSalmonellastrains were isolated from diverse poultry samples. MDR rates were high in serovarsS. enterica,S. typhimurium,S. enteritidis,S. arizonae,andS. gallinarum. Co-resistant to cefotaxime and ciprofloxacin in 56.4% ofSalmonellastrains was observed. Among 44 phenotypically ESBL-positiveSalmonellastrains, 36 (81.8%) carriedblaCTX-M and 38 (86%) carriedblaCTX-M-1. A High incidence rate ofblaCTX-M andbla-CTX-M-1 was observed amongS. enteritidis(19% and 21%),S. enterica(11% and 16%),S. typhimurium(13% and16%) andS. typhi(3% and 5%). Among 29 phenotypically MBL-positiveSalmonellastrains, 13 (44.8%) carriedblaVIM and 6 (20.6%) carriedblaIMP. The 67% prevalence ofgyrA was observed in fluoroquinolone-resistantSalmonellastrains. The most prevalent fluoroquinolone strains wereS. enteritidis(19%),S. typhimurium(19%),S. typhi(13%), andS. gallinarum(12%). Fluoroquinolone-resistant, MBL, and ESBL-producingSalmonella strainsfrom poultry are a matter of great concern for both livestock and public health, demonstrating the dissemination risk of these microorganisms through the food chain.
High-throughput two-photon volumetric brain imaging in freely moving mice
Authors: Qian Long , Liu Yaling , Chen Yalan , Wu Jianglai
Published: October 2024

Imaging neural activities across large volumes at subcellular resolution without impeding animal behaviors remains difficult. Here we introduce a high-throughput miniature Bessel-beam two-photon microscope capable of imaging calcium dynamics from neurons and dendrites over a volume of 420 × 420 × 80 μm³ during free behavior. We share full description of the microscope and demonstrate calcium imaging of more than 1000 neurons at a time in freely moving mice.
Transcriptomic atlas of the morphologic development of the fungal pathogenCoccidioidesreveals key phase-enriched transcripts
Authors: Homer Christina M. , Voorhies Mark , Walcott Keith , Ochoa Elena , Sil Anita
Published: October 2024

Coccidioides spp. are highly understudied but significant dimorphic fungal pathogens that can infect both immunocompetent and immunocompromised people. In the environment, they grow as multicellular filaments (hyphae) that produce vegetative spores called arthroconidia. Upon inhalation by mammals, arthroconidia undergo a process called spherulation. They enlarge and undergo numerous nuclear divisions to form a spherical structure, and then internally segment until the spherule is filled with multiple cells called endospores. Mature spherules rupture and release endospores, each of which can form another spherule, in a process thought to facilitate dissemination. Spherulation is unique toCoccidioidesand its molecular determinants remain largely unknown. Here, we report the first high-density transcriptomic analyses ofCoccidioidesdevelopment, defining morphology-dependent transcripts and those whose expression is regulated by Ryp1, a major regulator required for spherulation and virulence. Of approximately 9000 predicted transcripts, we discovered 273 transcripts with consistent spherule-associated expression, 82 of which areRYP1-dependent, a set likely to be critical forCoccidioidesvirulence. ChIP-Seq revealed 2 distinct regulons of Ryp1, one shared between hyphae and spherules and the other unique to spherules. Spherulation regulation was elaborate, with the majority of 227 predicted transcription factors inCoccidioidesdisplaying spherule-enriched expression. We identified provocative targets, including 20 transcripts whose expression is endospore-enriched and 14 putative secreted effectors whose expression is spherule-enriched, of which 6 are secreted proteases. To highlight the utility of these data, we selected a cluster ofRYP1-dependent, arthroconidia-associated transcripts and found that they play a role in arthroconidia cell wall biology, demonstrating the power of this resource in illuminatingCoccidioidesbiology and virulence.
Inconsistency of infant caretakers’ visual exposome with safe infant sleep recommendations: a systematic review and meta-analysis
Authors: de Visme Sophie , Pinhas Yaël , Cohen Jérémie F. , Moon Rachel Y. , Kanits Floortje , Plancoulaine Sabine , Sellier Anne-Laure , Harrewijn Inge , Gras-Le Guen Christèle , Chalumeau Martin
Published: October 2024

Importance

Rates of sudden unexpected death in infancy (SUDI) remain high in several high-income countries. Several studies reported rates of pictures of sleeping infants or infant sleeping environments that were highly inconsistent with safe infant sleep recommendations (SISRs) to prevent SUDI.

Objective

To provide robust and synthetized evidence to decision-makers involved in corrective actions, we systematically assessed the proportion of pictures that were inconsistent with SISRs in the visual exposome of infant caretakers.

Data Sources

In November 2023, we searched PubMed, Web of Science, and Google Scholar.

Study Selection

Eligible studies included were those reporting the quantitative evaluation of the inconsistency between one or several SISRs and pictures depicting sleeping infants or a sleeping environment intended for an infant in physical and digital public spaces.

Data Extraction and Synthesis

Data were extracted independently by 2 authors. The risk of bias of included studies was assessed with a customized version of Hoy’s tool for prevalence studies. A random-effects logistic regression model was used to obtain summary estimates of proportions of pictures. Between-study heterogeneity was estimated with theI2statistic.

Main Outcomes(s) and Measure(s)

The proportion of pictures inconsistent with one or several SISRs from the American Academy of Pediatrics.

Results

We screened 1,086 articles and included 7 studies conducted between 2008 and 2023 that analyzed pictures found in parenting magazines, online and print newspapers, baby diaper packaging, commercial stock photography websites, and Instagram. The overall risk of bias was deemed low. Among the 5,442 pictures depicting sleeping infants or infant sleep environments, the summary estimates of the proportion of inconsistencies with SISRs were 39% for a non-supine sleeping position, 5% for a soft sleeping surface, 8% for sharing the sleeping surface, 14% for an unsafe crib, 58% for soft objects or loose bedding, 17% for a covered head, and 85% for at least one SISR inconsistency. All summary estimates had significant between-study heterogeneity.

Conclusions and Relevance

Infant caretakers’ visual exposome is greatly inconsistent with SISRs and could lead to dangerous practices, which should prompt actions from manufacturers, advertisers, newspaper and website editors, social media moderators, and legislators.