bluuebunny/crossref_metadata_2025 huggingface dataset:
The past, present and future of Alzheimer's disease – part 1: the past
Authors: Nitrini Ricardo
Published: December 2023

Background Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases.

Objective To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD.

Methods A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021.

Results The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD.

Conclusion The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.
Advances in diffuse glial tumors diagnosis
Authors: Godoy Luis Filipe de Souza , Paes Vitor Ribeiro , Ayres Aline Sgnolf , Bandeira Gabriela Alencar , Moreno Raquel Andrade , Hirata Fabiana de Campos Cordeiro , Silva Frederico Adolfo Benevides , Nascimento Felipe , Campos Neto Guilherme de Carvalho , Gentil Andre Felix , Lucato Leandro Tavares , Amaro Junior Edson , Young Robert J. , Malheiros Suzana Maria Fleury
Published: December 2023

In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.
Long-term epilepsy associated-tumors (LEATs): what is new?
Authors: Rosemberg Sergio
Published: December 2023

Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.
Assessing the Capability of ChatGPT, Google Bard, and Microsoft Bing in Solving Radiology Case Vignettes
Authors: Sarangi Pradosh Kumar , Narayan Ravi Kant , Mohakud Sudipta , Vats Aditi , Sahani Debabrata , Mondal Himel
Published: December 2023

Background The field of radiology relies on accurate interpretation of medical images for effective diagnosis and patient care. Recent advancements in artificial intelligence (AI) and natural language processing have sparked interest in exploring the potential of AI models in assisting radiologists. However, limited research has been conducted to assess the performance of AI models in radiology case interpretation, particularly in comparison to human experts.

Objective This study aimed to evaluate the performance of ChatGPT, Google Bard, and Bing in solving radiology case vignettes (Fellowship of the Royal College of Radiologists 2A [FRCR2A] examination style questions) by comparing their responses to those provided by two radiology residents.

Methods A total of 120 multiple-choice questions based on radiology case vignettes were formulated according to the pattern of FRCR2A examination. The questions were presented to ChatGPT, Google Bard, and Bing. Two residents wrote the examination with the same questions in 3 hours. The responses generated by the AI models were collected and compared to the answer keys and explanation of the answers was rated by the two radiologists. A cutoff of 60% was set as the passing score.

Results The two residents (63.33 and 57.5%) outperformed the three AI models: Bard (44.17%), Bing (53.33%), and ChatGPT (45%), but only one resident passed the examination. The response patterns among the five respondents were significantly different (p = 0.0117). In addition, the agreement among the generative AI models was significant (intraclass correlation coefficient [ICC] = 0.628), but there was no agreement between the residents (Kappa = –0.376). The explanation of generative AI models in support of answer was 44.72% accurate.

Conclusion Humans exhibited superior accuracy compared to the AI models, showcasing a stronger comprehension of the subject matter. All three AI models included in the study could not achieve the minimum percentage needed to pass an FRCR2A examination. However, generative AI models showed significant agreement in their answers where the residents exhibited low agreement, highlighting a lack of consistency in their responses.
Electrophysiological evaluation of the neuromuscular junction: a brief review
Authors: Kouyoumdjian João Aris , Estephan Eduardo de Paula
Published: December 2023

The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability (“jiggle”) due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.
Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management
Authors: Teixeira Antonio Lucio , Rocha Natalia Pessoa , Gatchel Jennifer
Published: December 2023

Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of “mild behavioral impairment”, the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.
Outcomes of Patients with a Mechanical Heart Valve and Poor Anticoagulation Control on Warfarin
Authors: Johansson Isabelle , Benz Alexander P. , Kovalova Tanya , Balasubramanian Kumar , Fukakusa Bianca , Lynn Matthew J. , Nair Nikhil , Sikder Omaike , Patel Kashyap , Gayathri Sai , Robinson Marlene , Hardy Colin , Tyrwhitt Jessica , Schulman Sam , Eikelboom John W. , Connolly Stuart J.
Published: December 2023

Background Patients with a mechanical heart valve (MHV) require oral anticoagulation. Poor anticoagulation control is thought to be associated with adverse outcomes, but data are limited.

Objective To assess the risks of clinical outcomes in patients with a MHV and poor anticoagulation control on warfarin.

Methods We conducted a retrospective study of consecutive patients undergoing MHV implantation at a tertiary care center (2010–2019). Primary outcome was a composite of ischemic stroke, systemic embolism, or prosthetic valve thrombosis. Major bleeding and death were key secondary outcomes. We constructed multivariable regression models to assess the association between time in therapeutic range (TTR) on warfarin beyond 90 days after surgery with outcomes.

Results We included 671 patients with a MHV (80.6% in aortic, 14.6% in mitral position; mean age 61 years, 30.3% female). Median follow-up was 4.9 years, mean TTR was 62.5% (14.5% TTR <40%, 24.6% TTR 40–60%, and 61.0% TTR >60%). Overall rates of the primary outcome, major bleeding, and death were 0.73, 1.41, and 1.44 per 100 patient-years. Corresponding rates for patients with TTR <40% were 1.31, 2.77, and 3.22 per 100 patient-years. In adjusted analyses, every 10% decrement in TTR was associated with a 31% increase in hazard for the primary outcome (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.13–1.52), 34% increase in major bleeding (HR: 1.34, 95% CI: 1.17–1.52), and 32% increase in death (HR: 1.32, 95% CI: 1.11–1.57).

Conclusion In contemporary patients with a MHV, poor anticoagulation control on warfarin was associated with increased risks of thrombotic events, bleeding, and death.
Tissue clearing and imaging approaches for in toto analysis of the reproductive system
Authors: Folts Lillian , Martinez Anthony S , McKey Jennifer
Published: December 2023

New microscopy techniques in combination with tissue clearing protocols and emerging analytical approaches have presented researchers with the tools to understand dynamic biological processes in a three-dimensional context. This paves the road for the exploration of new research questions in reproductive biology, for which previous techniques have provided only approximate resolution. These new methodologies now allow for contextualized analysis of far-larger volumes than was previously possible. Tissue optical clearing and three-dimensional imaging techniques posit the bridging of molecular mechanisms, macroscopic morphogenic development, and maintenance of reproductive function into one cohesive and comprehensive understanding of the biology of the reproductive system. In this review, we present a survey of the various tissue clearing techniques and imaging systems, as they have been applied to the developing and adult reproductive system. We provide an overview of tools available for analysis of experimental data, giving particular attention to the emergence of artificial intelligence–assisted methods and their applicability to image analysis. We conclude with an evaluation of how novel image analysis approaches that have been applied to other organ systems could be incorporated into future experimental evaluation of reproductive biology.
Government, trusts, and the making of better roads in early nineteenth century England and Wales
Authors: Rosevear Alan , Bogart Dan , Shaw-Taylor Leigh
Published: December 2023

Who develops infrastructure? This paper introduces new data to explain which actors developed better roads in early nineteenth century England and Wales. We find that central Government sponsorship and financing of new roads was limited to 100 miles on sections of the politically important London-Holyhead Road. By comparison non-profit turnpike trusts made almost thirty times more new road mileage by attracting both public and private capital. Although the London-Holyhead Road had the highest quality, most turnpike trust roads were good. By government working with and through trusts, a better road network developed, especially in industrializing areas and along Mail routes.
Could 70 Be the New 60? Investigating the Association Between Internet Use and Subjective Age Among Chinese Older Adults
Authors: Zhao Menghan , Huang Yuanfeng , Zhang Youlang
Published: December 2023

Objectives

The widespread use of the Internet brings both opportunities and challenges for older adults. To understand its potential benefits and drawbacks, we focus on the association between Internet use and multiple indicators of subjective age (threshold age, felt age, and look age) and the underlying mechanisms.

Methods

A nationally representative sample of older adults aged 60 and over from 3 waves (collected in 2016, 2018, and 2020) of the China Longitudinal Aging Social Survey was used in the analysis. A 3-step random-effect model and mediation analysis were used to examine the relationship between Internet use and subjective age and the mediating roles of volunteering and feeling valued by society. Structural equation modeling with a serial multiple mediation model was conducted for robustness checks.

Results

The participants generally considered 70 as the threshold for “old age.” Although the mediation analysis did not show a significant indirect effect of Internet use on older adults’ subjective age through volunteering, Internet use was linked with older adults’ subjective age directly and indirectly through feeling valued by society. Compared to moderate Internet users, nonusers felt less valued by society and, therefore, had a younger threshold age and older subjective ages. Heavy Internet users showed a lower level of participation in volunteer activities.

Discussion

The results support previous theories about the mental and social health benefits of Internet use among older adults. However, Internet use intensity should receive more attention; excessive use may reduce the duration of older adults’ offline social interactions.
Music Engagement as Part of Everyday Life in Dementia Caregiving Relationships at Home
Authors: Allison Theresa A , Gubner Jennie M , Harrison Krista L , Smith Alexander K , Barnes Deborah E , Covinsky Kenneth E , Yaffe Kristine , Johnson Julene K
Published: December 2023

Background and Objectives

Emerging evidence suggests music-based interventions can improve the well-being of people living with dementia, but little is known about the ways in which music might support dementia caregiving relationships as part of everyday life at home. This study examined music engagement in the context of daily life to identify patterns of music engagement and potential targets for the design of music-based interventions to support well-being.

Research Design and Methods

This ethnographic, in-home study of people living with dementia and their family and professional care partners used methods from ethnomusicology, including semistructured interviews and in-home participant observation with a focus on music engagement.

Results

A total of 21 dyads were purposively recruited for diversity in terms of gender, ethnicity/race/heritage, caregiving relationship, and music experiences. Despite participants’ diverse music preferences, 3 distinct music engagement patterns emerged. (a) Professional care partners intentionally integrated music listening and singing into daily life as part of providing direct care. (b) Family care partners, who had prior dementia care nursing experience or family music traditions, integrated music into daily life in ways that supported their personal relationships. (c) In contrast, family care partners, who lacked dementia care experience and had high levels of caregiver burden, disengaged from prior music-making.

Discussion and Implications

The distinct music engagement patterns reflect different needs on the part of dyads. It is important to continue to support dyads who engage in music daily and to consider developing music-based interventions to support well-being among dyads who have become disengaged from music.
The symbolic consumption processes associated with ‘low-calorie’ and ‘low-sugar’ alcohol products and Australian women
Authors: Pitt Hannah , McCarthy Simone , Keric Danica , Arnot Grace , Marko Sarah , Martino Florentine , Stafford Julia , Thomas Samantha
Published: December 2023

The influence of commercial actors, practices and processes on the health and wellbeing of women is still not well understood. The alcohol industry has developed a range of products to appeal to new ‘health conscious’ markets, such as ‘low-calorie’ and ‘low-sugar’ products. While these products may have specific appeal for women, there has been little in-depth research that has sought to understand how women conceptualize these products and the range of symbolic meanings that women associate with these products. An online qualitatively led survey was conducted with n = 497 Australian women who had consumed alcohol in the last year. Questions related to the reasons for and influences on alcohol use, the purchasing of ‘low-calorie’ or ‘low-sugar’ products and the influence that these products might have on women’s alcohol use. Data were interpreted using reflexive thematic analysis. Women consumed alcohol to relax, cope with everyday stressors and because of the alignment with social practices and social connection. Women perceived that these products provided a healthier alternative to traditional alcohol products and that they aligned with women’s values relating to weight and the thin ideal. Some women were concerned that these products could increase alcohol consumption by reducing the perceptions of risk associated with alcohol. Policy consideration is needed to address how product claims and attributes may influence population groups’ interpretations of the risks and benefits of these alcohol products, including the illusion that these products have protective potential and are better for overall health and wellbeing.
Synergy of polymyxin B and minocycline against KPC-3- and OXA-48-producing Klebsiella pneumoniae in dynamic time–kill experiments: agreement with in silico predictions
Authors: Olsson Anna , Malmberg Christer , Zhao Chenyan , Friberg Lena E , Nielsen Elisabet I , Lagerbäck Pernilla , Tängdén Thomas
Published: December 2023

Objectives

Combination therapy is often used for carbapenem-resistant Gram-negative bacteria. We previously demonstrated synergy of polymyxin B and minocycline against carbapenem-resistant Klebsiella pneumoniae in static time–kill experiments and developed an in silico pharmacokinetic/pharmacodynamic (PK/PD) model. The present study assessed the synergistic potential of this antibiotic combination in dynamic experiments.

Methods

Two clinical K. pneumoniae isolates producing KPC-3 and OXA-48 (polymyxin B MICs 0.5 and 8 mg/L, and minocycline MICs 1 and 8 mg/L, respectively) were included. Activities of the single drugs and the combination were assessed in 72 h dynamic time–kill experiments mimicking patient pharmacokinetics. Population analysis was performed every 12 h using plates containing antibiotics at 4× and 8× MIC. WGS was applied to reveal resistance genes and mutations.

Results

The combination showed synergistic and bactericidal effects against the KPC-3-producing strain from 12 h onwards. Subpopulations with decreased susceptibility to polymyxin B were frequently detected after single-drug exposures but not with the combination. Against the OXA-48-producing strain, synergy was observed between 4 and 8 h and was followed by regrowth. Subpopulations with decreased susceptibility to polymyxin B and minocycline were detected throughout experiments. For both strains, the observed antibacterial activities showed overall agreement with the in silico predictions.

Conclusions

Polymyxin B and minocycline in combination showed synergistic effects, mainly against the KPC-3-producing K. pneumoniae. The agreement between the experimental results and in silico predictions supports the use of PK/PD models based on static time–kill data to predict the activity of antibiotic combinations at dynamic drug concentrations.
Diversity and evolutionary history of fossil crayfishes
Authors: Audo Denis , Hasiotis Stephen T , Kawai Tadashi
Published: December 2023

Freshwater crayfishes are among the most successful freshwater animals and are quite important for society economically, ecologically, and culturally. Since crayfishes are almost exclusively restricted to freshwater, their dispersion potential is much lower than that of marine crustaceans. Their biogeographic distribution is thus the result of a still poorly known long and complex evolutionary history. Most of the efforts made to untangle this history have worked from the distribution of extant crayfishes and their phylogenetic relationships, seldom using the fossil record. We here review the state of our current published knowledge on the fossil record of crayfishes, from their fossilized bodies and burrows. We review the Late Triassic Enoploclytia porteriMiller & Ash, 1988, one of the oldest crayfish body fossils, and show it is most likely a freshwater crayfish and assigned mistakenly to a marine genus. We also discuss burrows from Argentina, suggesting they are actually insect burrows, and burrows and an isolated claw from Libya, which we herein interpret as most likely from brachyuran crabs. We list a total of 65 occurrences or groups of occurrences from across the world and from the Late Devonian to Pleistocene fossils. This long history strengthens the current hypothesis that crayfishes inhabited Pangea and diversified partly via vicariance due to Pangea’s breakup during the Mesozoic and into the Cenozoic. Our review also highlights the importance of fossil burrows and body fossils to understand modern faunas and the importance of taxonomic revision of fossil taxa.
Seascape genomics of the pink abalone (Haliotis corrugata): An insight into a cross-border species in the northeast Pacific coast
Authors: Mares-Mayagoitia Jorge Alberto , Lafarga-De la Cruz Fabiola , Micheli Fiorenza , Cruz-Hernández Pedro , de-Anda-Montañez Juan A , Hyde John , Hernández-Saavedra Norma Y , Mejía-Ruíz Paulina , De Jesús-Bonilla Vladimir S , Vargas-Peralta Carmen E , Valenzuela-Quiñonez Fausto
Published: December 2023

Seascape genomics gives insight into the geographic and environmental factors shaping local adaptations. It improves the understanding of the potential effects of climate change, which is relevant to provide the basis for the international management of fishery resources. The pink abalone (Haliotis corrugata) is distributed from California, United States to Baja California Sur, Mexico, exposed to a latitudinal environmental gradient in the California Current System. Management of the pink abalone contrasts between Mexico and the United States; Mexico has an active fishery organized in four administrative areas, while the United States has kept the fishery in permanent closure since 1996. However, the impact of environmental factors on genetic variation along the species distribution remains unknown, and understanding this relationship is crucial for effective spatial management strategies. This study aims to investigate the neutral and adaptive genomic structure of H. corrugata. A total of 203 samples from 13 locations were processed using ddRADseq, and covering the species’ distribution. Overall, 2,231 neutral, nine potentially adaptive and three genomic–environmental association loci were detected. The neutral structure identified two groups: 1) California, United States and 2) Baja California Peninsula, México. In addition, the adaptive structure analysis also detected two groups with genetic divergence observed at Punta Eugenia. Notably, the seawater temperature significantly correlated with the northern group (temperate) and the southern (warmer) group. This study is a valuable foundation for future research and conservation initiatives, emphasizing the importance of considering neutral and adaptive genetic factors when developing management strategies for marine species.
Constructive theories through a modal lens
Authors: Tesi Matteo
Published: December 2023

We present a uniform proof-theoretic proof of the Gödel–McKinsey–Tarski embedding for a class of first-order intuitionistic theories. This is achieved by adapting to the case of modal logic the methods of proof analysis in order to convert axioms into rules of inference of a suitable sequent calculus. The soundness and the faithfulness of the embedding are proved by induction on the height of the derivations in the augmented calculi. Finally, we define an extension of the modal system for which the result holds with respect to geometric intuitionistic.
Transcriptome profiling and in silico docking analysis of phosphine resistance in rice weevil, Sitophilus oryzae (Coleoptera: Curculionidae)
Authors: Selvapandian Upasna , Nallusamy Saranya , Singh Sonu Kumar , Mannu Jayakanthan , Shanmugam Varanavasiappan , Ravikumar Caroline , Subbarayalu Mohankumar
Published: December 2023

The rice weevil, Sitophilus oryzae (Linnaeus, Coleoptera: Curculionidae), is a serious cosmopolitan pest that affects grain in storage and has developed high levels of resistance toward phosphine. In this study, RNA-seq data was used to study the phosphine resistance mechanisms in S. oryzae. Resistant and susceptible populations of S. oryzae were identified based on phosphine bioassays conducted in 32 populations collected across Tamil Nadu, India. Differential expression of mitochondrial (COX1, COX2, COX3, ND2, ND3, ATP6, and ATP8) and detoxification genes (Cyps, Gsts, and Cbe) were observed in the resistant and susceptible populations of S. oryzae. The previously characterized phosphine resistant gene, dld (dihydrolipoamide dehydrogenase) linked to the rph2 locus, was found to be up-regulated in resistant S. oryzae population (ISO-TNAU-RT) treated with phosphine. Also, the genes involved in Tricarboxylic acid (TCA) cycle were significantly down-regulated. In addition, a significant up-regulation in the expression of the antioxidant enzymes superoxide dismutase (2.5×) and catalase (2.1×) in ISO-TNAU-RT populations was recorded. Furthermore, a distinct amino acid substitution, Lysine > Glutamic acid (K141E) was identified in resistant phenotypes. In silico docking studies of both resistant and susceptible DLD protein with phosphine molecule revealed that the amino acid residues involved in the interaction were different. This suggested that the amino acid substitution might lead to structural modifications which reduces the affinity of the target (phosphine). This study provides insight on the various genes, pathways, and functional mechanisms having a significant role in phosphine resistance in S. oryzae.
Prevalence of germline BRCA1/2 pathogenic variants in Japanese patients treated with castration-resistant prostate cancer and efficacy of CRPC treatment in real-world clinical practice
Authors: Maekawa Shigekatsu , Takata Ryo , Sekiguchi Kie , Kagabu Masahiro , Toyoshima Moe , Tamada Shinji , Takahashi Kenta , Ikarashi Daiki , Matsuura Tomohiko , Kato Renpei , Kato Yoichiro , Kanehira Mitsugu , Sugimura Jun , Abe Takaya , Baba Tsukasa , Obara Wataru
Published: December 2023

Objective

The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer.

Methods

Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed.

Results

Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149).

Conclusions

In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.
A comparison of the population ecology of 4 Cryptomys hottentotus subspecies
Authors: Süess Tobias , Finn Kyle T , Janse van Vuuren Andries K , Hart Daniel W , Bennett Nigel C
Published: December 2023

Selection pressures underpinning the evolution of mammalian sociality and body mass variation have spurred great interest for several decades. Because they inhabit a wide range of geographic localities and habitats, African mole-rat subspecies of Cryptomys hottentotus present a unique opportunity to further our understanding of intra- and interspecific variation of sociality and body mass in mammalian species. We compared the demographics and body masses among 4 C. hottentotus subspecies: the Mahali mole-rat, C. h. mahali; highveld mole-rat, C. h. pretoriae; Natal mole-rat, C. h. natalensis; and common mole-rat, C. h. hottentotus within the context of their respective microclimates and evolutionary history. We propose that all ancestral C. hottentotus subspecies were arid-adapted and thus formed large colonies (as found today in the Mahali mole-rat). However, as the subspecies dispersed to occupy habitats of varying aridity and temperature across South Africa, selection for a particular colony size range in each subspecies arose to provide an adaptive fitness benefit to survive in its habitat. Consequently, the Mahali mole-rat—which remained in a warm and arid environment—retained the largest mean colony size, followed by the Natal mole-rat, which—even though inhabiting a hyper-mesic environment—selected for increased colony sizes to offset the energy requirement of thermoregulation (through huddling) in the cooler montane environments they prefer. The common mole-rat and the highveld mole-rat possessed the smallest mean colony sizes, likely the result of inhabiting a mesic and warm environment. At the same time, body mass variation in the C. hottentotus complex is likely linked to colony size variation, with subspecies having the largest colonies possessing the lowest individual body mass.
The mosquitoes (Diptera: Culicidae) of the Mexican Yucatan Peninsula: a comprehensive review on the use of taxonomic names
Authors: Talaga Stanislas , le Goff Gilbert , Arana-Guardia Roger , Baak-Baak Carlos Marcial , García-Rejón Julián Everardo , García-Suárez Omar , Rodríguez-Valencia Víctor Manuel , Tolsá-García María José , Suzán Gerardo , Roiz David
Published: December 2023

The Yucatan Peninsula is a biogeographic province of the Neotropical region which is mostly encompassed by the 3 Mexican states of Campeche, Quintana Roo, and Yucatán. During the development of the International Joint Laboratory ELDORADO (Ecosystem, bioLogical Diversity, habitat mOdifications and Risk of emerging PAthogens and Diseases in MexicO), a French–Mexican collaboration between the IRD (Institut de Recherche pour le Développement) and UNAM (Universidad Nacional Autónoma de México) in Mérida, it became evident that many putative mosquito species names recorded in the Mexican Yucatan Peninsula were misidentifications/misinterpretations or from the uncritical repetition of incorrect literature records. To provide a stronger foundation for future studies, the mosquito fauna of the Mexican Yucatan Peninsula is here comprehensively reviewed using current knowledge of taxonomy, ecology, and distribution of species through extensive bibliographic research, and examination of newly collected specimens. As a result, 90 mosquito species classified among 16 genera and 24 subgenera are recognized to occur in the Mexican Yucatan Peninsula, including 1 new peninsula record and 3 new state records.
NAC61 regulates late- and post-ripening osmotic, oxidative, and biotic stress responses in grapevine
Authors: Foresti Chiara , Orduña Luis , Matus José Tomás , Vandelle Elodie , Danzi Davide , Bellon Oscar , Tornielli Giovanni Battista , Amato Alessandra , Zenoni Sara
Published: December 2023

During late- and post-ripening stages, grape berry undergoes profound biochemical and physiological changes whose molecular control is poorly understood. Here, we report the role of NAC61, a grapevine NAC transcription factor, in regulating different processes involved in berry ripening progression. NAC61 is highly expressed during post-harvest berry dehydration and its expression pattern is closely related to sugar concentration. The ectopic expression of NAC61 in Nicotiana benthamiana leaves resulted in low stomatal conductance, high leaf temperature, tissue collapse and a higher relative water content. Transcriptome analysis of grapevine leaves transiently overexpressing NAC61 and DNA affinity purification and sequencing analyses allowed us to narrow down a list of NAC61-regulated genes. Direct regulation of the stilbene synthase regulator MYB14, the osmotic stress-related gene DHN1b, the Botrytis cinerea susceptibility gene WRKY52, and NAC61 itself was validated. We also demonstrate that NAC61 interacts with NAC60, a proposed master regulator of grapevine organ maturation, in the activation of MYB14 and NAC61 expression. Overall, our findings establish NAC61 as a key player in a regulatory network that governs stilbenoid metabolism and osmotic, oxidative, and biotic stress responses that are the hallmark of late- and post-ripening grape stages.
WISDOM Project - XVI. The link between circumnuclear molecular gas reservoirs and active galactic nucleus fuelling
Authors: Elford Jacob S , Davis Timothy A , Ruffa Ilaria , Bureau Martin , Cappellari Michele , Gensior Jindra , Iguchi Satoru , Liang Fu-Heng , Liu Lijie , Lu Anan , Williams Thomas G
Published: December 2023

We use high-resolution data from the millimetre-Wave Interferometric Survey of Dark Object Masses (WISDOM) project to investigate the connection between circumnuclear gas reservoirs and nuclear activity in a sample of nearby galaxies. Our sample spans a wide range of nuclear activity types including radio galaxies, Seyfert galaxies, low-luminosity active galactic nuclei (AGN) and inactive galaxies. We use measurements of nuclear millimetre continuum emission along with other archival tracers of AGN accretion/activity to investigate previous claims that at, circumnuclear scales (<100 pc), these should correlate with the mass of the cold molecular gas. We find that the molecular gas mass does not correlate with any tracer of nuclear activity. This suggests the level of nuclear activity cannot solely be regulated by the amount of cold gas around the supermassive black hole (SMBH). This indicates that AGN fuelling, that drives gas from the large-scale galaxy to the nuclear regions, is not a ubiquitous process and may vary between AGN type, with time-scale variations likely to be very important. By studying the structure of the central molecular gas reservoirs, we find our galaxies have a range of nuclear molecular gas concentrations. This could indicate that some of our galaxies may have had their circumnuclear regions impacted by AGN feedback, even though they currently have low nuclear activity. Alternatively, the nuclear molecular gas concentrations in our galaxies could instead be set by secular processes.
Hypoxia-induced galectin-8 maintains stemness in glioma stem cells via autophagy regulation
Authors: Liu Dan , Zhu Hongtao , Cheng Lidong , Li Ran , Ma Xiaoyu , Wang Jing , Wang Junwen , Zhang Suojun , Li Yingjie , Shu Kai , Yu Xingjiang , Li Chuanzhou
Published: December 2023

Background

Glioma stem cells (GSCs) are the root cause of relapse and treatment resistance in glioblastoma (GBM). In GSCs, hypoxia in the microenvironment is known to facilitate the maintenance of stem cells, and evolutionally conserved autophagy regulates cell homeostasis to control cell population. The precise involvement of autophagy regulation in hypoxic conditions in maintaining the stemness of GSCs remains unclear.

Methods

The association of autophagy regulation and hypoxia was first assessed by in silico analysis and validation in vitro. Glioma databases and clinical specimens were used to determine galectin-8 (Gal-8) expression in GSCs and human GBMs, and the regulation and function of Gal-8 in stemness maintenance were evaluated by genetic manipulation in vitro and in vivo. How autophagy was stimulated by Gal-8 under hypoxia was systematically investigated.

Results

Hypoxia enhances autophagy in GSCs to facilitate self-renewal, and Gal-8 in the galectin family is specifically involved and expressed in GSCs within the hypoxic niche. Gal-8 is highly expressed in GBM and predicts poor survival in patients. Suppression of Gal-8 prevents tumor growth and prolongs survival in mouse models of GBM. Gal-8 binds to the Ragulator-Rag complex at the lysosome membrane and inactivates mTORC1, leading to the nuclear translocation of downstream TFEB and initiation of autophagic lysosomal biogenesis. Consequently, the survival and proliferative activity of GSCs are maintained.

Conclusions

Our findings reveal a novel Gal-8-mTOR-TFEB axis induced by hypoxia in the maintenance of GSC stemness via autophagy reinforcement, highlighting Gal-8 as a candidate for GSCs-targeted GBM therapy.
Scientific objectives and payload configuration of the Chang'E-7 mission
Authors: Wang Chi , Jia Yingzhuo , Xue Changbin , Lin Yangting , Liu Jianzhong , Fu Xiaohui , Xu Lin , Huang Yun , Zhao Yufen , Xu Yigang , Gao Rui , Wei Yong , Tang Yuhua , Yu Dengyun , Zou Yongliao
Published: December 2023

As the cornerstone mission of the fourth phase of the Chinese Lunar Exploration Program, Chang'E-7 (CE-7) was officially approved, and implementation started in 2022, including a main probe and a communication relay satellite. The main probe, consisting of an orbiter, a lander, a rover and a mini-flying probe, is scheduled to be launched in 2026. The lander will land on Shackleton crater's illuminated rim near the lunar south pole, along with the rover and mini-flying probe. The relay satellite (named Queqiao-2) will be launched in February 2024 as an independent mission to support relay communication during scientific exploration undertaken by Chang’E-4, the upcoming Chang’E-6 in 2024 and subsequent lunar missions. The CE-7 mission is mainly aimed at scientific and resource exploration of the lunar south pole. We present CE-7’s scientific objectives, the scientific payloads configuration and the main functions for each scientific payload with its key technical specifications.
A Systematic Review of the Therapeutic Outcome of Mucormycosis
Authors: Sigera L Shamithra M , Denning David W
Published: December 2023

Background

Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes.

Methods

A systematic literature search using the Ovid MEDLINE and EMBASE databases identified manuscripts describing human mucormycosis diagnosed according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group criteria with therapeutic outcomes published from 2000 to 2022.

Results

In 126 articles, 10 335 patients were described, most from Asia (n = 6632, 66%). Diabetes was the most frequent underlying disease (n = 6188, 60%); 222 (2.1%) patients had no underlying diseases. The dominant clinical form was rhino-orbitocerebral (n = 7159, 69.3%), followed by pulmonary (n = 1062, 10.3%). Of 5364 patients with outcome data, amphotericin B monotherapy (n = 3749, mortality 31.5%) was most frequent, followed by amphotericin B + azole (n = 843, mortality 6.6%; P < .0001), amphotericin B followed by azole (n = 357, mortality 13.7%; P < .0001), posaconazole only (n = 250, mortality 17.2%; P < .0001), and isavuconazole only (n = 65, mortality 24.6%; P = .24). Duration and dose of antifungals varied widely. Documented outcomes from surgical resections in 149 patients found that 47 of 125 died (37.6%), compared with 16 of 24 (66.7%) patients who did not undergo surgery (P = .008).

Conclusions

Mucormycosis is more frequently reported in Asia than in Europe and is often linked to diabetes. Antifungal therapy, usually with surgery, is frequently effective for mucormycosis.
A Novel Germline Mutation of BRCA1 and Integrated Analysis With Somatic Mutation in a Chinese Multi-Cancer Family
Authors: Yang Xiling , Shang Li , Yang Liren , Sun Landi , Tuo Xiaoqian , Ma Sijia , Zhao Le , Li Xu , Yang Wenfang
Published: December 2023

The presence of mutations in the BRCA1 gene (MIM: 113705) is widely recognized as a significant genetic predisposition for ovarian cancer. This study investigated the genomic mutations in a Chinese family with a history of ovarian, breast, and rectal adenocarcinoma. A novel germline mutation (Phe1695Val) in BRCA1 was identified through whole-exome sequencing. Subsequently, we performed whole-genome sequencing to identify somatic mutations and analyze mutational signatures in individuals carrying the novel germline mutation. Our findings revealed a correlation between somatic mutational signatures and the BRCA1 germline mutation in the proband with ovarian cancer, while no such association was observed in the tumor tissue from the patient with breast cancer. Furthermore, distinct somatic driver mutations were identified, a truncated mutation in the TP53 gene in the ovarian tumor tissue, and a hotspot mutation in the PIK3CA gene in the breast cancer. According to our findings, the BRCA1 F1695V mutation is linked to ovarian cancer susceptibility in the family and causes specific somatic mutational profiles.
Development of a Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration of Imaging Features
Authors: Tran Cao Hop S , Witt Russell G , Elsayes Khaled M , Baiomy Ali A , Xiao Lianchun , Palmquist Sarah , Lee Sunyoung S , Mohamed Yehia I , Mahvash Armeen , Tzeng Ching-Wei D , Chun Yun Shin , Koay Eugene Jon , Rashid Asif , Hassan Manal M , Yao James C , Vauthey Jean-Nicolas , Kaseb Ahmed O
Published: December 2023

Background

Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods

Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created.

Results

We identified 383 patients with HCC with imaging and survival outcomes, n = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems.

Conclusions

Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC.