bluuebunny/crossref_metadata_2025 huggingface dataset:
RAD51 recruitment but not replication fork stability associates with PARP inhibitor response in ovarian cancer patient-derived xenograft models
Authors: Talens Francien , Teixeira Vivian Oliviera Nunes , Kok Yannick P , Chen Mengting , Rosenberg Efraim H , Debipersad Rashmie , Duiker Evelien W , van den Tempel Nathalie , Janatova Marketa , Zemankova Petra , Nederlof Petra M , Wisman G Bea A , Kleibl Zdenek , de Jong Steven , van Vugt Marcel A T M
Published: November 2024

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are currently used to treat BRCA1/2 mutant cancers. Although PARPi sensitivity has been attributed to homologous recombination (HR) defects, other roles of HR factors have also been linked to response to PARPi, including replication fork protection. In this study, we investigated PARPi sensitivity in ovarian cancer patient-derived xenograft (PDX) models in relation to HR proficiency and replication fork protection. Analysis of BRCA1/2 status showed that in our cohort of 31 ovarian cancer PDX models 22.6% harbored a BRCA1/2 alteration (7/31), and 48.3% (15/31) were genomically unstable as measured by copy number alteration analysis. In vivo, PARPi olaparib response was measured in 15 selected PDX models. Functional assessment of HR using ex vivo irradiation-induced RAD51 foci formation identified all olaparib-sensitive PDX models, including four models without BRCA1/2 alterations. In contrast, replication fork protection or replication speed in ex vivo tumor tissue did not correlate with olaparib response. Targeted panel sequencing in olaparib-sensitive models lacking BRCA1/2 alterations revealed a MUS81 variant as a possible mechanism underlying PARPi sensitivity. Combined, we show that ex vivo RAD51 analysis effectively predicts in vivo olaparib response and revealed a subset of PARPi-sensitive, HR-deficient ovarian cancer PDX models, lacking a BRCA1/2 alteration.
VILOCA: sequencing quality-aware viral haplotype reconstruction and mutation calling for short-read and long-read data
Authors: Fuhrmann Lara , Langer Benjamin , Topolsky Ivan , Beerenwinkel Niko
Published: November 2024

RNA viruses exist as large heterogeneous populations within their host. The structure and diversity of virus populations affects disease progression and treatment outcomes. Next-generation sequencing allows detailed viral population analysis, but inferring diversity from error-prone reads is challenging. Here, we present VILOCA (VIral LOcal haplotype reconstruction and mutation CAlling for short and long read data), a method for mutation calling and reconstruction of local haplotypes from short- and long-read viral sequencing data. Local haplotypes refer to genomic regions that have approximately the length of the input reads. VILOCA recovers local haplotypes by using a Dirichlet process mixture model to cluster reads around their unobserved haplotypes and leveraging quality scores of the sequencing reads. We assessed the performance of VILOCA in terms of mutation calling and haplotype reconstruction accuracy on simulated and experimental Illumina, PacBio and Oxford Nanopore data. On simulated and experimental Illumina data, VILOCA performed better or similar to existing methods. On the simulated long-read data, VILOCA is able to recover on average $82\%$ of the ground truth mutations with perfect precision compared to only $69\%$ recall and $68\%$ precision of the second-best method. In summary, VILOCA provides significantly improved accuracy in mutation and haplotype calling, especially for long-read sequencing data, and therefore facilitates the comprehensive characterization of heterogeneous within-host viral populations.
Predicting the pro-longevity or anti-longevity effect of model organism genes with enhanced Gaussian noise augmentation-based contrastive learning on protein–protein interaction networks
Authors: Alsaggaf Ibrahim , Freitas Alex A , Wan Cen
Published: November 2024

Ageing is a highly complex and important biological process that plays major roles in many diseases. Therefore, it is essential to better understand the molecular mechanisms of ageing-related genes. In this work, we proposed a novel enhanced Gaussian noise augmentation-based contrastive learning (EGsCL) framework to predict the pro-longevity or anti-longevity effect of four model organisms’ ageing-related genes by exploiting protein–protein interaction (PPI) networks. The experimental results suggest that EGsCL successfully outperformed the conventional Gaussian noise augmentation-based contrastive learning methods and obtained state-of-the-art performance on three model organisms’ predictive tasks when merely relying on PPI network data. In addition, we use EGsCL to predict 10 novel pro-/anti-longevity mouse genes and discuss the support for these predictions in the literature.
Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma
Authors: Rahmani Farzaneh , Camps Garrett , Mironchuk Olesya , Atagu Norman , Ballard David H , Benzinger Tammie L S , Chow Vincent Tze Yang , Dahiya Sonika , Evans John , Jaswal Shama , Hosseinzadeh Kassani Sara , Ma Da , Naeem Muhammad , Popuri Karteek , Raji Cyrus A , Siegel Marilyn J , Xu Yifei , Liu Jingxia , Beg Mirza Faisal , Chicoine Michael R , Ippolito Joseph E
Published: November 2024

Background

Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM).

Methods

We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS.

Results

Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores.

Conclusion

The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.
Hierarchical simplicial manifold learning
Authors: Zhang Wei , Shih Yi-Hsuan , Li Jr-Shin
Published: November 2024

Learning global structures, i.e. topological properties, inherent in complex data is an essential yet challenging task that spans across various scientific and engineering disciplines. A fundamental approach is to extract local data representations and use them to assemble the global structure. This conjunction of local and global operations catalyzes the integration of tools from algebraic and computational topology with machine learning. In this article, we propose a hierarchical simplicial manifold learning algorithm, constituted by nested clustering and topological reduction, for constructing simplicial complexes and decoding their topological properties. We show that the learned complex possesses the same topology as the original embedding manifold from which the data were sampled. We demonstrate applicability, convergence, and computational efficiency of the algorithm on both synthetic and real-world data.
Modeling long-term nutritional behaviors using deep homeostatic reinforcement learning
Authors: Yoshida Naoto , Arikawa Etsushi , Kanazawa Hoshinori , Kuniyoshi Yasuo
Published: November 2024

The continual generation of behaviors that satisfy all conflicting demands that cannot be satisfied simultaneously, is a situation that is seen naturally in autonomous agents such as long-term operating household robots, and in animals in the natural world. Homeostatic reinforcement learning (homeostatic RL) is known as a bio-inspired framework that achieves such multiobjective control through behavioral optimization. Homeostatic RL achieves autonomous behavior optimization using only internal body information in complex environmental systems, including continuous motor control. However, it is still unknown whether the resulting behaviors actually have the similar long-term properties as real animals. To clarify this issue, this study focuses on the balancing of multiple nutrients in animal foraging as a situation in which such multiobjective control is achieved in animals in the natural world. We then focus on the nutritional geometry framework, which can quantitatively handle the long-term characteristics of foraging strategies for multiple nutrients in nutritional biology, and construct a similar verification environment to show experimentally that homeostatic RL agents exhibit long-term foraging characteristics seen in animals in nature. Furthermore, numerical simulation results show that the long-term foraging characteristics of the agent can be controlled by changing the weighting for the agent’s multiobjective motivation. These results show that the long-term behavioral characteristics of homeostatic RL agents that perform behavioral emergence at the motor control level can be predicted and designed based on the internal dynamics of the body and the weighting of motivation, which change in real time.
Towards a Unitary Formulation of Quantum Field Theory in Curved Space-Time: The Case of the Schwarzschild Black Hole
Authors: Kumar K Sravan , Marto João
Published: November 2024

We argue that the origin of unitarity violation and the information loss paradox in our understanding of black holes (BHs) lies in the standard way of doing quantum field theory in curved space-time (QFTCS), which is heavily biased on intuition borrowed from classical general relativity. In this paper, with the quantum-first approach, we formulate a so-called direct-sum QFT (DQFT) in BH space-time based on a novel formulation of discrete space-time transformations in gravity that potentially restores unitarity. By invoking the quantum effects associated with the gravitational backreaction, we show that the Hawking quanta emerging outside of the Schwarzschild radius ($r_S=2GM$) cannot be independent of the quanta that continue to be inside $r_S$. This enables information to be carried by Hawking quanta, but in the BH DQFT formalism, we do not get any firewalls. Furthermore, DQFT leads to the BH evaporation involving only pure states. This means the quantum mechanical effects at the BH horizon produce two components of a maximally entangled pure state in geometric superselection sector Hilbert spaces. This construction enables pure states to evolve into pure states, restoring unitarity and observer complementarity. Finally, we discuss how our framework leaves important clues for formulating a scattering matrix and probing the nature of quantum gravity.
Decellularization of fish tissues for tissue engineering and regenerative medicine applications
Authors: Chen Wenhui , Chen Mengshi , Chen Siyi , Wang Siran , Huang Zijin , Zhang Lining , Wu Jiaming , Peng Weijie , Li Huaqiong , Wen Feng
Published: November 2024

Decellularization is the process of obtaining acellular tissues with low immunogenic cellular components from animals or plants while maximizing the retention of the native extracellular matrix structure, mechanical integrity and bioactivity. The decellularized tissue obtained through the tissue decellularization technique retains the structure and bioactive components of its native tissue; it not only exhibits comparatively strong mechanical properties, low immunogenicity and good biocompatibility but also stimulates in situ neovascularization at the implantation site and regulates the polarization process of recruited macrophages, thereby promoting the regeneration of damaged tissue. Consequently, many commercial products have been developed as promising therapeutic strategies for the treatment of different tissue defects and lesions, such as wounds, dura, bone and cartilage defects, nerve injuries, myocardial infarction, urethral strictures, corneal blindness and other orthopedic applications. Recently, there has been a growing interest in the decellularization of fish tissues because of the abundance of sources, less religious constraints and risks of zoonosis transmission between mammals. In this review, we provide a complete overview of the state-of-the-art decellularization of fish tissues, including the organs and methods used to prepare acellular tissues. We enumerated common decellularized fish tissues from various fish organs, such as skin, scale, bladder, cartilage, heart and brain, and elaborated their different processing methods and tissue engineering applications. Furthermore, we presented the perspectives of (i) the future development direction of fish tissue decellularization technology, (ii) expanding the sources of decellularized tissue and (iii) innovating decellularized tissue bio-inks for 3D bioprinting to unleash the great potential of decellularized tissue in tissue engineering and regenerative medicine applications.
Clinical and Functional Outcomes of Community-Recruited Individuals at Clinical High-Risk for Psychosis: Results From the Youth Mental Health Risk and Resilience Study (YouR-Study)
Authors: Haining Kate , Gajwani Ruchika , Gross Joachim , Gumley Andrew I , Lawrie Stephen M , Schultze-Lutter Frauke , Schwannauer Matthias , Uhlhaas Peter J
Published: November 2024

Clinical high-risk for psychosis (CHR-P) individuals are typically recruited from clinical services but the clinical and functional outcomes of community-recruited CHR-P individuals remain largely unclear. The Youth Mental Health Risk and Resilience Study (YouR-Study) obtained a community sample of CHR-P individuals through an online-screening approach and followed-up these individuals for a period of up to 3 years to determine transition rates, persistence of attenuated psychotic symptoms (APS) and functional outcomes. Baseline data were obtained from n = 144 CHR-P participants, n = 51 participants who met online cutoff criteria but not CHR-P criteria (CHR-Ns), and n = 58 healthy controls. Baseline assessments included clinical measures for assessing CHR-P status, including the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult version (SPI-A), as well as functioning and cognitive measures. CHR-P and CHR-N groups were followed-up. Results show that 12.1% of CHR-P individuals transitioned to psychosis over 3 years, with no transitions in the CHR-N group. Nearly 60% of CHR-P individuals experienced poor functional outcome (PFO) and over 40% experienced persistent APS. A combination of CAARMS/SPI-A criteria was associated with a higher likelihood of PFO, but not with transition to psychosis nor APS persistence. However, transition risk was generally higher among those meeting both CAARMS/SPI-A criteria (64.3%) vs CAARMS (28.6%) or SPI-A (7.1%) alone. In summary, community-recruited CHR-P individuals are characterized by similar clinical characteristics and longitudinal outcomes to those recruited from clinical services, emphasizing the need to widen the scope of early detection and intervention strategies.
Challenges and strategies for implementing the STAR tool for comprehensive evaluation of guidelines: A qualitative study with Chinese clinicians
Authors: Yang Nan , Wang Xu , He Hongfeng , Zhao Jungang , Qin Yishan , Li Yueyan , Estill Janne , Wei Junmin , Chen Yaolong
Published: November 2024

Background:

The STAR (Scientific, Transparent, and Applicable rankings) working group conducts regular evaluations of Chinese guidelines and consensus statements. This study gathered insights from STAR working group members using qualitative interviews.

Methods:

From March to August 2023, members of the STAR specialist committees were interviewed using semi-structured interview outline. The interviewees were selected through purpose-based sampling. Subject analysis was employed to summarize the findings.

Results:

We conducted interviews with 37 members from 36 committees and summarized the contents into four main themes and 16 specific topics. The value of STAR in enhancing the development and selection of high-quality guidelines in China was commonly mentioned. Challenges identified included the lack of resources and suboptimal organizational structures, collaboration, and evaluation efficiency. Suggestions for the STAR tool included developing extensions for different guideline types, adjusting certain items, and better covering guideline applicability. The promotion of STAR and the consideration of an international committee for global outreach were also highlighted.

Conclusion:

STAR has exerted a substantial influence on the evaluation of Chinese guidelines, and the insights gained from interviews offer valuable directions for its further enhancement.
Preventing the Re-emergence of Deadly Nipah Virus
Authors: Tyagi Satvik , Sahai Sanjeev , Upadhyay Shalini
Published: November 2024

The Indo-Bangladesh region frequently suffers from periodic Nipah virus (NiV) outbreaks. NiV is a zoonotic agent that can be transmitted from animals to humans and also from humans to humans. NiV infections may cause deadly neurological dysfunctions with a fatality rate of up to 75%. Various methods have been developed to diagnose NiV infections at different stages of the disease, but there is currently no specific antiviral treatment or vaccine available. NiV outbreaks are mostly endemic; however, the high susceptibility of the human population, high mutation rates of the viral RNA genome and the possibility of human-to-human transmission in this era of globalization enable NiV to potentially cause a pandemic. To prevent serious consequences of NiV outbreaks, international deliberation on risk assessment, investigation of the molecular and genetic aspects of NiV, pertinent measures of surveillance and framing of general guidelines for its management should be integrated. This review underlines the basic information available in the literature and its application for further research to reach a solution for mitigation of such catastrophic infections.
Food for thought: optimal diet in patients with asthma and chronic obstructive pulmonary disease
Authors: Vameghestahbanati Motahareh , Wang Carolyn J. , Sin Don D.
Published: November 2024

Purpose of review

Nutritional intake plays a major role in the management of lung health. This review provides the latest perspective on how dietary choices can modulate lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma.

Recent findings

The pathophysiology of COPD and asthma is driven by oxidative stress and inflammation of the airways, which is exacerbated by modifiable risk factors such as cigarette smoking and diet. Various foods can influence patient symptoms; highly processed foods increase the production of reactive oxygen species that augment airway inflammation, whereas foods rich in antioxidants, fiber and protein combat oxidative stress and muscle wastage. Patients with COPD or asthma are at increased risk of developing metabolic comorbidities, including cachexia and obesity that complicate disease phenotypes, leading to greater symptom severity. While clinical findings suggest a role for antioxidant and macronutrient support of lung function, comprehensive translational and clinical studies are necessary to better understand the mechanisms underlying nutrient interaction and lung structure–function.

Understanding the nutritional requirements that protect lung health and support weight management in COPD and asthma is imperative to providing personalized dietary recommendations and reducing patient morbidity.
Radioactive iodine therapy dose impact on recurrence and survival in N1 papillary thyroid cancer
Authors: Odil Elizabeth E. , Ward Katelyn R. , Davis Ryan T. , Reilly Jordan M. , Sun Fionna , Elassar Heba , Lapkus Morta , Pastewski Jacquelyn , Studzinski Diane M. , Callahan Rose E. , Czako Peter F. , Nagar Sapna
Published: November 2024

Objective

The objective of this study is to investigate radioactive iodine therapy (RAIT) dose impact on survival and recurrence in patients with papillary thyroid cancer (PTC) with regional lymph node metastasis (N1).

Methods

A retrospective study of PTC patients with N1 disease from 2007 to 2011 at a tertiary academic hospital collected demographics, tumor characteristics, and RAIT treatment dose. RAIT dose was stratified by total dosage less than or greater than 150 mCi. Outcomes included recurrence, immediate RAIT side-effects, and mortality.

Results

A total of 60 N1a and 21 N1b patients were studied with a median follow-up of about 9 years. No statistically significant differences were found between N1a PTC patients who received high-dose vs low-dose RAIT in recurrence rate (6.9% vs 6.7%, P > 0.999) or immediate RAIT side effects (6.9% vs 16.1%, P = 0.426). There were no mortalities in the N1a group. For patients with N1b PTC, there were no differences between high-dose and low-dose RAIT in recurrence rate (41.7% vs 44.4%, P > 0.999), mortality (0% vs 16.7%, P = 0.375), or immediate RAIT side effects (8.3% vs 11.1%, P > 0.999).

Conclusion

Dosages of RAIT ≥ 150 mCi do not appear to provide additional benefit in reducing recurrence compared to doses <150 mCi for N1a or N1b PTC patients. No differences in mortality or immediate RAIT side effects were observed between the two dosing regimens; however, interpretation is limited by low event rates. Large randomized trials are needed for further individualized recommendations regarding optimal RAIT dosage in N1 PTC.
Prostatectomy and other local treatments for oligometastatic prostate cancer: recent and ongoing trials
Authors: Fang Andrew M. , MacDonald Landan P. , Gregg Justin R. , Siddiqui Bilal A. , Tang Chad , Chapin Brian F.
Published: November 2024

Purpose of review

Oligometastatic prostate cancer (OMPCa) is an intermediary state between localized and disseminated metastatic disease that has historically been treated with androgen deprivation therapy (ADT) and more recently with additional systemic therapies in combinations. However, cytoreductive control of the primary tumor may offer an opportunity to control the disease and enhance the response from systemic treatment. In this review, the use of local therapy to the prostate including cytoreductive prostatectomy (CRP), whole pelvis radiotherapy (RT), and focal therapies will be evaluated in the treatment of patients with newly diagnosed OMPCa.

Recent findings

Retrospective studies have demonstrated that some patients with OMPCa may indeed benefit from CRP. With preliminary trials demonstrating that CRP is safe and feasible, there are several phase II and III trials that are currently underway to investigate the role of CRP among patients with OMPCa. Results from several clinical trials have demonstrated that RT and ADT may benefit patients with OMPCa. Lastly, the evidence for focal and cryotherapy remains limited and further clinical trials are required.

OMPCa is a unique disease state that may benefit from local therapy to the primary tumor. Further study is required to guide treatment selection and patient candidacy. Several trials specifically are awaited to better define the treatment options for patients.
Use and Perceptions of Mobile Mental Health Applications Among Healthcare Workers in Saudi Arabia
Authors: Almadani Ahmad H. , Aldawood Buthainah D. , Alahmari Faysal M. , AbuDujain Nasser M. , Otayf Mojahed M.
Published: November 2024

The use and perceptions of smartphone-based mental health applications (MH-Apps) in Saudi Arabia require exploration. This study investigated MH-App use among Saudi Arabian healthcare workers (HCWs), including psychiatrists, psychologists, and family medicine physicians. It also assessed HCWs' interest in and willingness to integrate these apps into their practices, as well as their cognitive flexibility and its relationship with their attitudes and app use. This cross-sectional study involved 386 participants recruited using convenience and snowball sampling. The Cognitive Flexibility Scale (CFS) was used to assess cognitive flexibility. The results showed that 33.2% of HCWs downloaded MH-Apps, with 67.9% considering them somewhat beneficial. However, most had not yet tried them. Only 7% of HCWs strongly agreed that these apps are evidence-based. Concerns about using these apps in their practices were reported by 36.5% of HCWs, with the most common concern being the lack of evidence-based support. The primary reason for downloading MH-Apps for personal use was to improve mental well-being, whereas patient-related use was psychoeducation. Furthermore, 27.5% of HCWs recommended MH-Apps to their patients, with old age, women, and psychiatrists/psychologists more likely to recommend them. Higher CFS scores were more strongly associated with older HCWs, those who had ever recommended MH-Apps, and those who used the apps. Saudi Arabian HCWs should be encouraged to use and recommend MH-Apps, with more evidence-based research needed to address concerns. Further research on cognitive flexibility's implications for clinical practice is also warranted.
Finite Element Analysis of the Influence of the Z-Shaped Position of Cleft lip on the Postoperative Appearance
Authors: Liang Hao , Shi Yuejie , Zhai Weigui , Li Haidong
Published: November 2024

In traditional surgery for patients with secondary deformities of cleft lip, the skin is usually cut open, and forceps are used according to the position of the flap. However, this method cannot predict the postoperative effect before surgery, especially the changes in the patient’s lip. Moreover, in surgery, the design of the surgical flap is also quite random, needing more quantitative standards for its position and size, which makes it impossible to optimize the surgical effect, resulting in the surgical effect relying on the surgeon’s surgical level. In this study, we attempted to scan the patient’s face using infrared scanning equipment, establish a three-dimensional model of the patient’s face, and compare the postoperative effects under different surgical positions through finite element analysis, especially comparing the displacement of the affected labial peak point to find the optimal surgical plan. In this way, the authors can predict the surgical effect before cleft lip and cleft palate surgery so that patients can directly see the effect after surgery and choose the most suitable scheme.
Recurrent Nasal Subcutaneous Emphysema: A Rare Complication of Open Septorhinoplasty
Authors: Wimbiscus Mae A. , Alter Noah E. , Savitz Benjamin L. , Cornley Ronald M. , Abbott Erin N. , Gutama Barite W. , Torres-Guzman Ricardo A. , Garner Desmond , Lineaweaver William C. , Patel Priyesh N.
Published: November 2024

Subcutaneous emphysema (SE) is a notably rare complication of surgical procedures, particularly in the context of rhinoplasty. In this report, we present a novel case of recurrent nasal SE following routine open septorhinoplasty in a 59-year-old male. This patient developed persistent subcutaneous air over the nasal dorsum, linked to a fistula tract to the nasal vault, despite initial conservative management with needle aspiration. The patient required surgical intervention to repair the mucosalized fistula tract, leading to a successful long-term outcome. This case highlights a significant gap in the current understanding of SE, as previous reports have primarily focused on periorbital involvement rather than nasal SE and underscores the importance of recognizing nasal SE as a potential complication of rhinoplasty.
Evaluating Cephalic Index Changes in Sagittal Synostosis Surgery: A Retrospective Study of Subtotal Versus Total Vault Remodeling
Authors: Kurzbuch Arthur R. , Cooper Ben , Duncan Christian , Ellenbogen Jonathan , Vakharia Vejay , Hennedige Anusha , Parks Chris , Sinha Ajay
Published: November 2024

Scaphocephaly is the most common form of craniosynostosis, characterized by premature closure of the sagittal suture. Surgical intervention is the standard treatment, aimed at correcting cranial shape and improving the cephalic index (CI), the key metric to quantify postsurgical outcomes. Controversies exist in the literature regarding the optimal timing of surgery and the choice of surgical technique. At our center, children aged 6 to 24 months presenting with sagittal synostosis and frontal bossing without significant occipital bullet undergo subtotal (anterior 2/3) vault remodeling, whereas those with both occipital bullet and frontal bossing are treated with total vault remodeling. This retrospective monocenter study tracks the progression of CI in pediatric patients undergoing these 2 techniques at 3 timepoints. From 2007 to 2015 the authors operated on 32 patients, excluding syndromic cases and reoperations. Twenty-three patients underwent subtotal and 9 total vault remodeling. The mean age at surgery was 12.66 months (range 6–24 months). The CI improved significantly in all patients after surgery. Overall, the CI increased from 66.67% preoperatively to 76.67% postoperatively and to 76.83% at 4 years. In the subtotal vault remodeling group, CI increased from 67.27% to 76.81% postoperatively, reaching 77.27% at 4 years. In the total vault remodeling group, CI rose from 65.11% to 76.29% postoperatively but decreased to 75.07% at 4 years. The authors' data show a sustained improvement in CI postoperatively, with a slight reduction in the total vault remodeling group at long-term follow-up.
Is Zika virus re-emerging as a distinct genetic lineage in India?
Authors: N Pradeep Kumar , P M Ajith Lal , Saini Prasanta , S Aiswarya R , Suresh Abidha , Samuel Philip , R Balasubramaniam , Mathew Jessu , T Sonia , K P Amju , K H K Raju , A Veerapathiran , A Selvam , T Balaji , Kumar Ashwani
Published: November 2024

An outbreak of Zika fever occurred in Thiruvananthapuram City, Kerala, India during 2021. On request of the Kerala state health administration, we investigated the same, towards proposing requisite containment strategies of the disease outbreak. Epidemiological investigations indicated a clustering pattern of Zika fever cases with the presumed index case from a multi-speciality hospital in the city. Preliminary reports on the same had been already reported elsewhere during 2021. Further, entomological surveys carried out evinced the predominant mosquito species in the City viz., Aedes albopictus (65.55%), Aedes aegypti (22.0%) and Aedes vittatus (12.0%) were naturally infected with Zika virus (ZIKV), the Minimum Infection Rates (MIR) being 17.9, 7.8 and 3.6 respectively. Also, trans-ovarian transmission was recorded in Ae. albopictus. This is the first report on detection of ZIKV from Ae. albopictus in India. Analysis of phylogenetically informative genes of ZIKV genome indicated the emergence of a distinct lineage of the Asian strain of virus, with five unique non-synonymous mutations viz., “A22T” & “I160M” (pre-Membrane) and “D348N”, “T470A” & “V473L” (Envelope). was involved in the outbreak. The altered gene expression pattern and evolutionary implications of these unique mutations remain to be investigated. Genetic analysis of the virus isolates from this and other investigations carried out on sporadic outbreaks of ZIKV in the country subsequently, indicated ZIKV is reemerging as a distinct genetic lineage in India. These findings and other recent reports on ZIKV outbreaks warrant an urgent need for a systematic country-wide surveillance strategy, towards the prevention/ preparedness/ containment of a massive outbreak of this emerging neurovirulent arboviral disease.
Stage-specific CAR-mediated signaling generates naïve-like, TCR-null CAR T cells from induced pluripotent stem cells
Authors: Yoo Sang Pil , Yuan Xuegang , Engstrom Claire , Chang Patrick , Li Suwen , Lathrop Lindsay , Lagosh Jessica , Seet Christopher , Kohn Donald B. , Crooks Gay M.
Published: November 2024

Genetically modified, induced pluripotent stem cells (iPSCs) offer a promising allogeneic source for the generation of functionally enhanced, chimeric antigen receptor (CAR) T cells. However, the signaling of CARs during early T cell development and the removal of the endogenous T cell receptor required to prevent alloreactivity pose significant challenges to the production of mature conventional CAR T cells from iPSCs. Here, we show that TCR-null, CD8αβ CAR T cells can be efficiently generated from iPSCs by engineering stage-specific onset of CAR expression and signaling to both permit conventional T cell development and to induce efficient positive selection. CAR T cells produced using this approach displayed a uniform, naïve T cell phenotype and demonstrated superior antigen-specific cytotoxicity compared to iPSC-derived effector memory CAR T cells. Multimodal sequencing revealed CAR-mediated positive selection induced the persistent upregulation of key transcription factors involved in naïve T cell development. Achieving precise control of CAR expression and signaling in developmentally sensitive T precursors will be critical to realizing the full potential for “off-the-shelf”, iPSC-derived cellular therapies.
Bacterial communities associated with food-quality winter pea cultivars grown in Pacific Northwest soils
Authors: Yurgel Svetlana N. , McGee Rebecca
Published: November 2024

Background and aims

Breeding legume for improved yield and seed quality, coupled with extensive use of fertilization may disrupt the ability of modern cultivars to interact with native microbiome. Autumn-sown food-quality winter pea (WP) represent new crop in the Pacific Northwest (PNW). However, little is known about the ability of these cultivars to establish associations with bacteria native to PNW soils.

Methods

We evaluated soil, root and nodule microbiomes associated with four WP cultivars in diverse locations across Washington state with the goal to better understand the interaction occurring between WP cultivars and bacterial communities native to PNW soils.

Results

Root and nodule microbiomes were affected by sampling event, while plant genotype only affected nodule microbiome. A diverse population of native rhizobia colonized WP roots, while a smaller subset of these bacteria colonized WP nodules. Three rhizobial ASVs had relatively low abundance in the soils but were dominant in nodule-associated microbiome regardless of the variation of soil parameters between locations, indicating their strong attraction to host-plant nodules. Several non-rhizobial taxa were apparently enriched in nodules. However, in-depth study of legume root and nodule microbiome is required to better understand interactions within this complex phytobiome.

Conclusion

WP cultivars can form nodules in PNS soils in fall, but environmental factors have a strong effect on this process. While the complementation of legume nodule microbiome with root-associated microbiome analysis might be a useful tool, studies focusing on mature nodules with increased depth of sequencing might provide a better resolution of nodule-specific residents.
Molecular characterization of the archaic HLA-B*73:01 allele reveals presentation of a unique peptidome and skewed engagement by KIR2DL2
Authors: Ross Philipp , Hilton Hugo G. , Lodwick Jane , Slezak Tomasz , Guethlein Lisbeth A. , McMurtrey Curtis P. , Han Alex S. , Nielsen Morten , Yong Daniel , Dulberger Charles L. , Nolan Kristof T. , Roy Sobhan , Castro Caitlin D. , Hildebrand William H. , Zhao Minglei , Kossiakoff Anthony , Parham Peter , Adams Erin J.
Published: November 2024

HLA class I alleles of archaic origin may have been retained in modern humans because they provide immunity against diseases to which archaic humans had evolved resistance. According to this model, archaic introgressed alleles were somehow distinct from those that evolved in African populations. Here we show that HLA-B*73:01, a rare allotype with putative archaic origins, has a relatively rare peptide binding motif with an unusually long-tailed peptide length distribution. We also find that HLA-B*73:01 combines a restricted and unique peptidome with high-cell surface expression, characteristics that make it well-suited to combat one or a number of closely-related pathogens. Furthermore, a crystal structure of HLA-B*73:01 in complex with KIR2DL2 highlights differences from previously solved structures with HLA-C molecules. These molecular characteristics distinguish HLA-B*73:01 from other HLA class I alleles previously investigated and may have provided early modern human migrants that inherited this allele with a selective advantage as they colonized Europe and Asia.
The identification of a SARs-CoV2 S2 protein-derived peptide with super-antigen-like stimulatory properties on T-cells
Authors: Tu Thai Hien , Bennani Fatima Ezzahra , Masroori Nasser , Liu Chen , Nemati Atena , Rozza Nicholas , Grunbaum Amichai Meir , Kremer Richard , Milhalcioiu Catalin , Roy Denis-Claude , Rudd Christopher
Published: November 2024

Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3). Computational modeling predicts P3 binding to sites on MHC class I/II and the TCR that partially overlap with sites for the binding of staphylococcal enterotoxins B and H. Like SEB and SEH peptides, P3 stimulated 25-40% of human CD4+ and CD8+ T cells, increasing IFN-γ and granzyme B production. viSNE and SPADE profiling identified overlapping and distinct IFN-γ and GZMB subsets. The super-antigenic properties of P3 were further evident by its selective expansion of T cells expressing specific TCR Vα and Vβ chain repertoires. In vivo experiments in mice revealed that the administration of P3 led to a significant upregulation of proinflammatory cytokines IL-1β, IL-6, and TNF-α. While the clinical significance of P3 in COVID-19 remains unclear, its homology to other mammalian proteins suggests a potential role for this peptide family in human inflammation and autoimmunity.
Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability
Authors: Dürauer Sophie , Kang Hyun-Seo , Wiebeler Christian , Machida Yuka , Schnapka Dina S , Yaneva Denitsa , Renz Christian , Götz Maximilian J , Weickert Pedro , Major Abigail C , Rahmanto Aldwin S , Gutenthaler-Tietze Sophie M , Daumann Lena J , Beli Petra , Ulrich Helle D , Sattler Michael , Machida Yuichi J , Schwierz Nadine , Stingele Julian
Published: November 2024

The DNA-dependent protease SPRTN maintains genome stability by degrading toxic DNA-protein crosslinks (DPCs). To understand how SPRTN’s promiscuous protease activity is confined to the cleavage of crosslinked proteins, we reconstitute the repair of DPCs including their modification with SUMO and ubiquitin chains, using recombinant human proteins. We discover that DPC ubiquitylation strongly activates SPRTN independently of SPRTN’s known ubiquitin-binding domains. Using protein structure prediction, MD simulations and NMR spectroscopy we reveal that ubiquitin binds to an interface at the back of SPRTN’s protease domain, promoting an active conformation. Replacing key interfacial residues prevents ubiquitin-dependent activation of SPRTN, which leads to genomic instability and cell cycle defects in cells expressing hypomorphic SPRTN variants that cause premature aging and liver cancer in Ruijs-Aalfs syndrome patients. Collectively, our results demonstrate that SPRTN activation is coupled to the modification of the crosslinked protein, explaining how specificity is achieved during DPC repair.
Effect of tryptophan starvation on inclusion membrane composition and chlamydial-host interactions
Authors: Riffaud-Widner Camille M. , Widner Ray E. , Ouellette Scot P. , Rucks Elizabeth A.
Published: November 2024

Chlamydiais an obligate intracellular bacterial pathogen that develops within a membrane-bound vacuole called an inclusion. Throughout its developmental cycle,Chlamydiamodifies the inclusion membrane (IM) with type III secreted (T3S) membrane proteins, known as inclusion membrane proteins (Incs). Via the IM,Chlamydiamanipulates the host cell to acquire lipids and nutrients necessary for its growth. One key nutrient is tryptophan (Trp). As a Trp auxotroph,Chlamydiais very sensitive to Trp starvation and, in response to low Trp levels induced by the immune response, enters a viable but nonreplicating state called persistence. To maintain viability during persistence,Chlamydiamust necessarily maintain both the integrity of the IM and its ability to modify host cell responses, but how Trp starvation affects IM composition and subsequent interactions with the host cell remains poorly understood. We hypothesize that, under Trp starvation conditions, Inc expression/stability or T3S function during persistence alters IM composition but that key host-Chlamydiainteractions will be preserved. To examine host-Chlamydiainteractions during persistence, we examined sphingomyelin, cholesterol, and transferrin trafficking to the inclusion, as well as localization of host proteins that bind to specific Incs. We identified IM composition changes during persistence by monitoring endogenous Inc abundance at the IM. Chlamydial T3S is generally functional during persistence. Specific changes in Inc composition in the IM can be linked to Trp content of a specific Inc or effector-specific defects in chlamydial T3S. Overall, our findings reveal that critical host-Chlamydiainteractions are maintained during persistence mediated by Trp starvation.
Treatment and reprocessing of textile dyeing wastewater by using the electrocoagulation treatment process
Authors: Fatima Noor , Shaikh Irfan Ahmad
Published: November 2024

This study electrocoagulated textile effluent to remove dyes. The wastewater reuse method was used to study three reactive dyes: C.I. Reactive Red 221, Blue 19, and Yellow 145. Laboratory wastewater was electrocoagulated. Standard wastewater had three pH values. (4, 7, 10). Electrocoagulation removes volatile dye colors well. The best results were 98% within 15-20 minutes for 1% C.I. Reactive Red 221. After 20 minutes, 1% shade C.I. Reactive Blue 19 and Yellow 145 color removal efficacy is 96%. Electrocoagulation treatment of dyeing effluent is greatly affected by pH. Electrocoagulation efficacy was lowest at pH 4. When pH was highest, removal efficacy was best. Dyeing wastewater removal efficiency improved when pH was changed from 7 to 10. Discolored wash-off cloth batches were rubbed dry and wet. The normal and electro-coagulant treated wash-off batches had wash fastness and rubbing values of 4 to 5 in dry crocking. The C.I. Reactive Dyes (Red 221, Yellow 145, and Blue 19) standard fabrics and treated wash-off with electro-coagulated lot showed 3 to 4 wet rubbing, almost like the standard fabric, but no shade changes at this concentration. All three reactive dyes had color values. Because alkaline pH removes dyes best, color difference values of Batch C (fabric treated by pH 10 wash-off) were within the approved range of 0.38 to 1.50 of all dyes and shades (5%,3%,1%). Batch A values between 2.44 and 13.48 were outside the allowed range (< 1). Batch B (fabric treated by pH 7 wash-off) values fell between Batch A and Batch C.
Stereoselectivity of Aminoacyl-RNA Loop-closing Ligation
Authors: Kim Shannon , Todisco Marco , Radakovic Aleksandar , Szostak Jack W.
Published: November 2024

The origin of amino acid homochirality remains an unresolved question in the origin of life. The requirement of enantiopure nucleotides for nonenzymatic RNA copying strongly suggests that homochirality of nucleotides and RNA arose early. However, this leaves open the question of whether and how homochiral RNA subsequently imposed biological homochirality on other metabolites including amino acids. Previous studies have reported moderate stereoselectivity for various aminoacyl-RNA transfer reactions. Here we examine aminoacyl-RNA loop-closing ligation, a reaction that ‘captures’ aminoacylated RNA in a stable phosphoramidate product, such that the amino acid bridges two nucleotides in the RNA backbone. We find that the rate of this reaction is much higher for RNA aminoacylated with L-amino acids than D-amino acids. We present an RNA sequence that near-exclusively captures L-amino acids in loop-closing ligation. Finally, we demonstrate that ligation of aminoacyl-L-RNA results in inverse stereoselectivity for D-amino acids. The observed stereochemical link between D-RNA and L-amino acids in the synthesis of RNA stem-loops containing bridging amino acids constitutes a stereoselective structure building process. We suggest that this process led to a selection for the evolution of aminoacyl-RNA synthetase ribozymes that were selective for L-amino acids, thereby setting the stage for the subsequent evolution of homochiral peptide and ultimately protein synthesis.
Investigating lncRNAs at different levels of parasitism in parasitic plants
Authors: Rodrigues Wenderson Felipe Costa , Pires Laura Oliveira , Del-Bem Luiz-Eduardo , Ishida Juliane Karine
Published: November 2024

Parasitic plants exhibit unique adaptations, including specialized structures like haustoria and reduced organs. We analyzed genomic and transcriptomic data from nine parasitic species across hemi-, holo-, and endoparasitic lifestyles, uncovering distinct patterns of lncRNA abundance and expression. Holoparasites exhibited the highest lncRNA counts, while endoparasites displayed notable reductions. Expression analyses revealed tissue-specific patterns, with elevated lncRNA activity in haustorial tissues ofCuscuta. Phylogenetic analyses suggested horizontal gene transfer (HGT) of lncRNA sequences, particularly inSapria. These findings highlight the potential involvement of lncRNAs in parasitic plant adaptation, host interaction, and genomic evolution through HGT.