bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review and meta-analysis of neuromodulation therapies for substance use disorders
Authors: Mehta Dhvani D. , Praecht Angela , Ward Heather B. , Sanches Marcos , Sorkhou Maryam , Tang Victor M. , Steele Vaughn R. , Hanlon Colleen A. , George Tony P.
Published: December 2023

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge’s g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.
A global synthesis and assessment of free-ranging domestic cat diet
Authors: Lepczyk Christopher A. , Fantle-Lepczyk Jean E. , Dunham Kylee D. , Bonnaud Elsa , Lindner Jocelyn , Doherty Tim S. , Woinarski John C. Z.
Published: December 2023

Free-ranging cats (Felis catus) are globally distributed invasive carnivores that markedly impact biodiversity. Here, to evaluate the potential threat of cats, we develop a comprehensive global assessment of species consumed by cats. We identify 2,084 species eaten by cats, of which 347 (16.65%) are of conservation concern. Islands contain threefold more species of conservation concern eaten by cats than continents do. Birds, reptiles, and mammals constitute ~90% of species consumed, with insects and amphibians being less frequent. Approximately 9% of known birds, 6% of known mammals, and 4% of known reptile species are identified in cat diets. 97% of species consumed are <5 kg in adult body mass, though much larger species are also eaten. The species accumulation curves are not asymptotic, indicating that our estimates are conservative. Our results demonstrate that cats are extreme generalist predators, which is critical for understanding their impact on ecological systems and developing management solutions.
Structure and activation mechanism of the Makes caterpillars floppy 1 toxin
Authors: Belyy Alexander , Heilen Philipp , Hagel Philine , Hofnagel Oliver , Raunser Stefan
Published: December 2023

The bacterial Makes caterpillars floppy 1 (Mcf1) toxin promotes apoptosis in insects, leading to loss of body turgor and death. The molecular mechanism underlying Mcf1 intoxication is poorly understood. Here, we present the cryo-EM structure of Mcf1 from Photorhabdus luminescens, revealing a seahorse-like shape with a head and tail. While the three head domains contain two effectors, as well as an activator-binding domain (ABD) and an autoprotease, the tail consists of two putative translocation and three putative receptor-binding domains. Rearrangement of the tail moves the C-terminus away from the ABD and allows binding of the host cell ADP-ribosylation factor 3, inducing conformational changes that position the cleavage site closer to the protease. This distinct activation mechanism that is based on a hook-loop interaction results in three autocleavage reactions and the release of two toxic effectors. Unexpectedly, the BH3-like domain containing ABD is not an active effector. Our findings allow us to understand key steps of Mcf1 intoxication at the molecular level.
Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population
Authors: Simms Kate T. , Keane Adam , Nguyen Diep Thi Ngoc , Caruana Michael , Hall Michaela T. , Lui Gigi , Gauvreau Cindy , Demke Owen , Arbyn Marc , Basu Partha , Wentzensen Nicolas , Lauby-Secretan Beatrice , Ilbawi Andre , Hutubessy Raymond , Almonte Maribel , De Sanjosé Silvia , Kelly Helen , Dalal Shona , Eckert Linda O. , Santesso Nancy , Broutet Nathalie , Canfell Karen
Published: December 2023

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix, to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63–67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO’s updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.
Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV
Authors: Hall Michaela T. , Simms Kate T. , Murray John M. , Keane Adam , Nguyen Diep T. N. , Caruana Michael , Lui Gigi , Kelly Helen , Eckert Linda O. , Santesso Nancy , de Sanjose Silvia , Swai Edwin E. , Rangaraj Ajay , Owiredu Morkor Newman , Gauvreau Cindy , Demke Owen , Basu Partha , Arbyn Marc , Dalal Shona , Broutet Nathalie , Canfell Karen
Published: December 2023

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform (‘Policy1-Cervix-HIV’) to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7–33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3–5 years.
Talin and kindlin use integrin tail allostery and direct binding to activate integrins
Authors: Aretz Jonas , Aziz Masood , Strohmeyer Nico , Sattler Michael , Fässler Reinhard
Published: December 2023

Integrin affinity regulation, also termed integrin activation, is essential for metazoan life. Although talin and kindlin binding to the β-integrin cytoplasmic tail is indispensable for integrin activation, it is unknown how they achieve this function. By combining NMR, biochemistry and cell biology techniques, we found that talin and kindlin binding to the β-tail can induce a conformational change that increases talin affinity and decreases kindlin affinity toward it. We also discovered that this asymmetric affinity regulation is accompanied by a direct interaction between talin and kindlin, which promotes simultaneous binding of talin and kindlin to β-tails. Disrupting allosteric communication between the β-tail-binding sites of talin and kindlin or their direct interaction in cells severely compromised integrin functions. These data show how talin and kindlin cooperate to generate a small but critical population of ternary talin–β-integrin–kindlin complexes with high talin–integrin affinity and high dynamics.
Research and engineering practice on space characteristics of gangue slurry filling
Authors: Gu Wenzhe , Yang Baogui , Pan Hao , Song Tianqi
Published: December 2023

The macroscopic characteristics of the fractured space and the microscopic pore features are critical factors determining the effectiveness of gangue slurry backfilling. To identify the key areas for slurry backfilling, a combination of theoretical analysis, simulation experiments, and on-site industrial trials was used to reveal the movement laws of backfilling space overlying the fractured zone. The distribution characteristics of voids available for slurry backfilling within the fractured space were explored, and the interaction between gangue slurry and goaf voids was clarified. A formula for calculating the void ratio in the caved zone was derived, and a model for the distribution of voids in the slurry backfilling space was established. This model identified the main areas where slurry backfilling should be focused, namely the overlapping space between the free accumulation zone and the load-influenced zone. Experimental results demonstrated that the porosity of the collapsed rock mass within the goaf follows a negative logarithmic function along both the dip and strike directions, which was consistent with the theoretical calculations. Through in-situ grouting backfilling experiments on the ground, the feasibility of gangue slurry backfilling in the goaf was verified, and the process of interaction between gangue slurry and goaf voids was elaborated. This process generally involves three stages: initial flow, vertical upwelling, and horizontal diffusion, all of which are closely interconnected. Practical engineering applications of gangue slurry backfilling were carried out in the free accumulation zone and the load-influenced zone at the Huangling No. 2 coal mine. The successful validation of underground gangue slurry backfilling technology demonstrated its feasibility and the correctness of the theoretical approach. This research provides new evidence for environmentally friendly disposal of gangue materials.
Structural and biophysical comparisons of the pomalidomide- and CC-220-induced interactions of SALL4 with cereblon
Authors: Ma Xiaolei , Leon Barbara , Ornelas Elizabeth , Dovala Dustin , Tandeske Laura , Luu Catherine , Pardee Gwynn , Widger Stephania , Solomon Jonathan M. , Beckwith Rohan E. J. , Moser Heinz , Clifton Matthew C. , Wartchow Charles A.
Published: December 2023

The design of cereblon-binding molecular glues (MGs) that selectively recruit a desired protein while excluding teratogenic SALL4 is an area of significant interest when designing therapeutic agents. Previous studies show that SALL4 is degraded in the presence of IKZF1 degraders pomalidomide, and to a lesser extent by CC-220. To expand our understanding of the molecular basis for the interaction of SALL4 with cereblon, we performed biophysical and structural studies demonstrating that SALL4 zinc finger domains one and two (ZF1-2) interact with cereblon (CRBN) in a unique manner. ZF1 interacts with the N-terminal domain of cereblon and ZF2 binds as expected in the C-terminal IMiD-binding domain. Both ZF1 and ZF2 contribute to the potency of the interaction of ZF1-2 with CRBN:MG complexes and the affinities of SALL4 ZF1-2 for the cereblon:CC-220 complex are less potent than for the corresponding pomalidomide complex. Structural analysis provides a rationale for understanding the reduced affinity of SALL4 for cereblon in the presence of CC-220, which engages both ZF1 and ZF2. These studies further our understanding of the molecular glue-mediated interactions of zinc finger-based proteins with cereblon and may provide structural tools for the prospective design of compounds with reduced binding and degradation of SALL4.
DC-electrical penetration graph waveforms for Dalbulus maidis (Hemiptera: Cicadellidae) and the effects of entomopathogenic fungi on its probing behavior
Authors: Maluta Nathalie , Castro Thiago , Spotti Lopes João Roberto
Published: December 2023

The corn leafhopper Dalbulus maidis is an important transmitter of viruses and bacteria to maize plants. Data on the stylet probing and ingestion behavior of D. maidis, gathered using the DC-electrical penetration graph (DC-EPG) technique, are limited. The increasing prevalence of this pest and the diseases that it transmits in maize crops heighten the importance of studying how control tools affect the probing behavior of these insects, to reduce or prevent the chances of pathogen transmission and the damage from feeding. Our study recorded stylet activities of D. maidis, using a DC-EPG system and compared the appearances of waveforms with those from published AC and AC-DC EPG studies. All types of systems produced similar waveform appearances; therefore, we used the waveform nomenclature previously published. We also determined the effects of the entomopathogenic fungus Cordyceps javanica on the probing behavior of D. maidis at different time points after the fungus was applied by spraying. Forty-eight hours after the insects were sprayed, the effects were pronounced, with significant disruption of the stylet activities in phloem and non-phloem phases. Our study indicated that this commercial microbiological product, with the active ingredient C. javanica, can alter the probing behavior of D. maidis and may be helpful in management of the vector.
Associations between recollected rates of Category D fruit machine use as a child and adult gambling in a young adult sample
Authors: Newall Philip
Published: December 2023

There have been recent restrictions to the range of gambling products made available to UK children, with the industry association Bacta introducing a minimum age of 18 for Category D fruit machines, which can otherwise be legally used by children. Any potential government action on Category D fruit machines may want to consider limitations in the current evidence base. The present study addressed this issue, by conceptually replicating previous results associating recollected usage of Category D fruit machine usage as a child and adult gambling. Compared to previous studies, the present study used a younger adult sample, and also tested for potential moderation by subjective confidence. Three out of four main tested associations were significant and in the hypothesised direction, and a lack of significance on interaction terms yielded no evidence of potential moderation by subjective confidence. The present study therefore added to the limited evidence base on potential risks of legal Category D fruit machine usage as a child.
Calcium phosphate ceramics combined with rhBMP6 within autologous blood coagulum promote posterolateral lumbar fusion in sheep
Authors: Ivanjko Natalia , Stokovic Nikola , Pecin Marko , Vnuk Drazen , Smajlovic Ana , Ivkic Niko , Capak Hrvoje , Javor Ana , Vrbanac Zoran , Maticic Drazen , Vukicevic Slobodan
Published: December 2023

Posterolateral spinal fusion (PLF) is a procedure used for the treatment of degenerative spine disease. In this study we evaluated Osteogrow-C, a novel osteoinductive device comprised of recombinant human Bone morphogenetic protein 6 (rhBMP6) dispersed in autologous blood coagulum with synthetic ceramic particles, in the sheep PLF model. Osteogrow-C implants containing 74–420 or 1000–1700 µm ceramic particles (TCP/HA 80/20) were implanted between L4–L5 transverse processes in sheep (Ovis Aries, Merinolaandschaf breed). In the first experiment (n = 9 sheep; rhBMP6 dose 800 µg) the follow-up period was 27 weeks while in the second experiment (n = 12 sheep; rhBMP6 dose 500 µg) spinal fusion was assessed by in vivo CT after 9 weeks and at the end of the experiment after 14 (n = 6 sheep) and 40 (n = 6 sheep) weeks. Methods of evaluation included microCT, histological analyses and biomechanical testing. Osteogrow-C implants containing both 74–420 and 1000–1700 µm ceramic particles induced radiographic solid fusion 9 weeks following implantation. Ex-vivo microCT and histological analyses revealed complete osseointegration of newly formed bone with adjacent transverse processes. Biomechanical testing confirmed that fusion between transverse processes was complete and successful. Osteogrow-C implants induced spinal fusion in sheep PLF model and therefore represent a novel therapeutic solution for patients with degenerative disc disease.
Effect of Pd/Pt decoration on MoSSe monolayer for CH4 signature through surface adsorption mechanism
Authors: Babariya Bindiya , Gupta Sanjeev K. , Gajjar P. N.
Published: December 2023

Considering the current breakthrough in gas sensor technology, we have examined impact of CH4 in the vicinity of pristine MoSSe and Pd/Pt decorated MoSSe monolayers using first principles approach. The negative formation energies confirm structural stability of considered monolayers. The pristine MoSSe monolayer is semiconductor having 1.52 eV direct band gap. This value decreases in the presence of Pd/Pt adatom. Further, adsorption strength of CH4 to monolayers is validated by sensing parameters such as adsorption energy, recovery time, charge transfer and work function. Though we found maximum adsorption energies of − 0.674 and − 0.636 eV for adsorption on Se site of Pd/Pt decorated MoSSe monolayers, the overall sensing response also reveals high sensitivity for Se surface. However, both sites S and Se are favorable for CH4 adsorption. When CH4 is activated on Pd/Pt decorated monolayers, band gaps vary with marginal alterations and transform to direct type. Moreover, optical dielectric response alters strongly in the visible region after activation of CH4 on to Pd/Pt decorated MoSSe monolayers. This result identifies sensitivity response in the presence of methane which may detect CH4 gas easily in visible region. Generally, these interesting results of methane sensing study provoke Pd/Pt decorated MoSSe monolayers to be good sensing nano-device.
Research on the localized lightfield features of metallic nano-cone-tip optical antenna via investigating near-field lightwave and correlated net-charge distribution
Authors: Liu Taige , Shi Jiashuo , Duan Shenghua , Ji Wuyang , Wang Zhe , Zhang Xinyu
Published: December 2023

In this paper, the near-field lightwave characteristics of an arrayed silicon nano-cone-tip optical antenna (NOA) covered by a common metal film, which can be viewed as a featured quasi quantum dot (QD), are carefully investigated. A dipole net-charge distribution closely correlated with the surface lightwaves excited over the antennas by incident lasers with a central wavelength of 633 nm, is clearly observed. An obvious Coulomb-like blockade from the apex apparently influencing the net-charge converging over the surface of NOA, is verified, which can also be predicted by the simulations according to surface standing waves across the apex node. The antinodes of the surface net-charge instantaneous distribution are already pushed away from the normal location owing to the apex Coulomb-like blockade, so as to present a distorted waveform different from traditional standing wave modes. The tip proximity effect leading to a relatively weak net-charge converging over surrounding planar facet and adjacent NOAs, is also discovered.
Characterization of durum wheat resistance against leaf rust under climate change conditions of increasing temperature and [CO2]
Authors: Porras Rafael , Miguel-Rojas Cristina , Lorite Ignacio J. , Pérez-de-Luque Alejandro , Sillero Josefina C.
Published: December 2023

Durum wheat cultivation in Mediterranean regions is threatened by abiotic factors, mainly related to the effects of climate change, and biotic factors such as the leaf rust disease. This situation requires an in-depth knowledge of how predicted elevated temperatures and [CO2] will affect durum wheat-leaf rust interactions. Therefore, we have characterised the response of one susceptible and two resistant durum wheat accessions against leaf rust under different environments in greenhouse assays, simulating the predicted conditions of elevated temperature and [CO2] in the far future period of 2070–2099 for the wheat growing region of Cordoba, Spain. Interestingly, high temperature alone or in combination with high [CO2] did not alter the external appearance of the rust lesions. However, through macro and microscopic evaluation, we found some host physiological and molecular responses to infection that would quantitatively reduce not only pustule formation and subsequent infection cycles of this pathogen, but also the host photosynthetic area under these predicted weather conditions, mainly expressed in the susceptible accession. Moreover, our results suggest that durum wheat responses to infection are mainly driven by temperature, being considered the most hampering abiotic stress. In contrast, leaf rust infection was greatly reduced when these weather conditions were also conducted during the inoculation process, resembling the effects of possible heat waves not only in disease development, but also in fungal germination and penetration success. Considering this lack of knowledge in plant-pathogen interactions combined with abiotic stresses, the present study is, to the best of our knowledge, the first to include the effects of the expected diurnal variation of maximum temperature and continuous elevated [CO2] in the durum wheat-leaf rust pathosystem.
Level I of evidence does not support manual lymphatic drainage for total knee arthroplasty: a meta-analysis
Authors: Migliorini Filippo , Schäfer Luise , Bertini Francesca Alzira , Memminger Michael Kurt , Simeone Francesco , Giorgino Riccardo , Maffulli Nicola
Published: December 2023

It is unclear whether manual lymphatic drainage (MLD) following primary total knee arthroplasty (TKA) is effective in reducing pain and swelling and improving knee function. The present study investigated the efficacy of MLD after TKA. The outcomes of interest are the range of motion (ROM), pain (visual analogue scale, VAS), and circumference of the lower leg. This meta-analysis was conducted according to the 2020 PRISMA statement. In November 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase, with no time constraint. Only level I evidence studies, according to the Oxford Centre of Evidence-Based Medicine, were considered. All the randomised controlled trials (RCTs) comparing patients who have received MLD versus a group of patients who did not undergo MLD following primary TKA were accessed. Data from four RCTs (197 TKAs) were retrieved. 67% (132 of 197 patients) were women. The mean length of follow-up was 7.0 ± 5.8 weeks. The mean age of the patients was 69.6 ± 2.7 years, and the mean BMI was 28.7 ± 0.9 kg/m2. At baseline, between-group comparability was evidenced in the male:female ratio, mean age, mean BMI, knee flexion, and VAS. No difference was found in flexion (P = 0.7) and VAS (P = 0.3). No difference was found in the circumference of the thigh (P = 0.8), knee (P = 0.4), calf (P = 0.4), and ankle (P = 0.3). The current level I of evidence does not support the use of MLD in primary TKA.
A noval pulmonary function evaluation method based on ResNet50 + SVR model and cough
Authors: Xu Wenlong , He Guoqiang , Shen Dan , Xu Bingqiao , Jiang Peirong , Liu Feng , Lou Xiaomin , Guo Lingling , Ma Li
Published: December 2023

Traditionally, the clinical evaluation of respiratory diseases was pulmonary function testing, which can be used for the detection of severity and prognosis through pulmonary function parameters. However, this method is limited by the complex process, which is impossible for patients to monitor daily. In order to evaluate pulmonary function parameters conveniently with less time and location restrictions, cough sound is the substitute parameter. In this paper, 371 cough sounds segments from 150 individuals were separated into 309 and 62 as the training and test samples. Short-time Fourier transform (STFT) was applied to transform cough sound into spectrogram, and ResNet50 model was used to extract 2048-dimensional features. Through support vector regression (SVR) model with biological attributes, the data were regressed with pulmonary function parameters, FEV1, FEV1%, FEV1/FVC, FVC, FVC%, and the performance of this models was evaluated with fivefold cross-validation. Combines with deep learning and machine learning technologies, the better results in the case of small samples were achieved. Using the coefficient of determination (R2), the ResNet50 + SVR model shows best performance in five basic pulmonary function parameters evaluation as FEV1(0.94), FEV1%(0.84), FEV1/FVC(0.68), FVC(0.92), and FVC%(0.72). This ResNet50 + SVR hybrid model shows excellent evaluation of pulmonary function parameters during coughing, making it possible to realize a simple and rapid evaluation for pneumonia patients. The technology implemented in this paper is beneficial in judge the patient's condition, realize early screening of respiratory diseases, evaluate postoperative disease changes and detect respiratory infectious diseases without time and location restrictions.
Stability of Feline Coronavirus in aerosols and dried in organic matrices on surfaces at various environmental conditions
Authors: Reissner Janina , Siller Paul , Bartel Alexander , Roesler Uwe , Friese Anika
Published: December 2023

Enveloped respiratory viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be transmitted through aerosols and contact with contaminated surfaces. The stability of these viruses outside the host significantly impacts their transmission dynamics and the spread of diseases. In this study, we investigated the tenacity of Feline Coronavirus (FCoV) in aerosols and on surfaces under varying environmental conditions. We found that airborne FCoV showed different stability depending on relative humidity (RH), with higher stability observed at low and high RH. Medium RH conditions (50–60%) were associated with increased loss of infectivity. Furthermore, FCoV remained infectious in the airborne state over 7 h. On stainless-steel surfaces, FCoV remained infectious for several months, with stability influenced by organic material and temperature. The presence of yeast extract and a temperature of 4 °C resulted in the longest maintenance of infectivity, with a 5 log10 reduction of the initial concentration after 167 days. At 20 °C, this reduction was achieved after 19 days. These findings highlight the potential risk of aerosol and contact transmission of respiratory viruses, especially in enclosed environments, over extended periods. Studying surrogate viruses like FCoV provides important insights into the behavior of zoonotic viruses like SARS-CoV-2 in the environment.
Investigating the prognostic value of mTORC1 signaling in bladder cancer via bioinformatics evaluation
Authors: Yu Xin , Li Wenge , Sun Shengrong , Li Juanjuan
Published: December 2023

Bladder cancer, a prevalent and heterogeneous malignancy, necessitates the discovery of pertinent biomarkers to enable personalized treatment. The mammalian target of rapamycin complex 1 (mTORC1), a pivotal regulator of cellular growth, metabolism, and immune response, exhibits activation in a subset of bladder cancer tumors. In this study, we explore the prognostic significance of mTORC1 signaling in bladder cancer through the utilization of bioinformatics analysis. Our investigation incorporates transcriptomic, somatic mutation, and clinical data, examining the mTORC1 score of each sample, as well as the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. Our findings reveal that elevated mTORC1 levels serve as an adverse prognostic indicator for bladder cancer patients, exhibiting a significant association with Basal-type bladder cancer. Patients with heightened mTORC1 activation display heightened levels of pro-carcinogenic metabolism. Additionally, these individuals demonstrate enhanced response to immunotherapy. Finally, we develop an mTORC1-related signature capable of predicting the prognosis of bladder cancer patients.The signature offers novel mTORC1-related biomarkers and provides fresh insights into the involvement of mTORC1 in the pathogenesis of bladder cancer.
Insight into chloroplast genome structural variation of the Mongolian endemic species Adonis mongolica (Ranunculaceae) in the Adonideae tribe
Authors: Nyamgerel Nudkhuu , Baasanmunkh Shukherdorj , Oyuntsetseg Batlai , Bayarmaa Gun-Aajav , Erst Andrey , Park Inkyu , Choi Hyeok Jae
Published: December 2023

Adonis mongolicais a threatened species that is endemic to Mongolia. It is a medicinal plant from theAdonisgenus and has been used to treat heart diseases. However, the genomics and evolution of this species have not been thoroughly studied. We sequenced the first complete plastome ofA. mongolicaand compared it with ten Adonideae species to describe the plastome structure and infer phylogenetic relationships. The complete plastome ofA. mongolicawas 157,521 bp long and had a typical quadripartite structure with numerous divergent regions. The plastomes of Adonideae had relatively constant genome structures and sizes, except for those ofAdonis. The plastome structure was consistent acrossAdonis. We identified a 44.8 kb large-scale inversion within the large single-copy region andrpl32 gene loss in theAdonisplastomes compared to other members of the Adonideae tribe. Additionally,Adonishad a smaller plastome size (156,917–157,603 bp) than the other genera within the tribe (159,666–160,940 bp), which was attributed to deletions of intergenic regions and partial and complete gene losses. These results suggested that an intramolecular mutation occurred in the ancestor of theAdonisgenus. Based on the phylogenetic results,Adonisseparated earlier than the other genera within the Adonideae tribe. The genome structures and divergences of specific regions in theAdonisgenus were unique to the Adonideae tribe. This study provides fundamental knowledge for further genomic research in Mongolia and a better understanding of the evolutionary history of endemic plants.
Clinical correlation of cholelithiasis in patients undergoing percutaneous endoscopic gastrostomy
Authors: Cha Boram , Lee Jungnam , Lee Jaehyuk , Park Jin-Seok , Jeong Seok , Lee Don Haeng
Published: December 2023

The risk factor for cholelithiasis include low physical activity. With an aging society, the number of bedridden patients who undergo percutaneous endoscopic gastrostomy (PEG) has increased, and cholelithiasis has often been found in these patients. This study aimed to evaluate the risk factors correlated with cholelithiasis in adults who underwent PEG. This retrospective single-center design study reviewed patients who underwent PEG and were confirmed to have cholelithiasis through imaging from March 1996 to December 2021. The investigated variables were age, sex, body mass index (BMI, kg/m2), cause of PEG insertion, initial physical activity status, laboratory findings on PEG insertion day, and incidence of acute cholecystitis. The differences between categorical and continuous variables were analyzed using Student’s t test and chi-square test. We enrolled 576 eligible patients who underwent PEG insertion. A total of 161 patients were detected with cholelithiasis (28.0%). The overall independent risk factors for cholelithiasis in patients who underwent PEG insertion were increased C-reactive protein (CRP) levels and decreased physical activity status (bedridden state). The incidence of cholelithiasis was increased by up to 30.7%, especially in patients with bedridden status. However, the incidence of acute cholecystitis among cholelithiasis group was only 5.6%. BMI and total cholesterol were positively correlated with the size of gallbladder (GB) stones. One of the major risk factors for cholelithiasis is decreased physical activity, especially in patients who underwent PEG insertion. Abdominal imaging is recommended to confirm the presence of cholelithiasis and to consider prophylaxis for cholelithiasis, especially in bedridden patients with elevated initial CRP levels at the time of PEG insertion.
Prehabilitative high-intensity interval training and resistance exercise in patients prior allogeneic stem cell transplantation
Authors: Kuehl Rea , Feyer Jule , Limbach Matthias , Pahl Antonia , Stoelzel Friederike , Beck Heidrun , Wegner Annika , Rosenberger Friederike , Dreger Peter , Luft Thomas , Wiskemann Joachim
Published: December 2023

Physical capacity prior allogeneic stem cell transplantation (allo-HCT) has been shown as a relevant prognostic factor for survival after transplant. Therefore, we evaluated feasibility and preliminary efficacy of a high-intensity interval training (HIIT) and moderate to high-intensity resistance exercise (RE) to increase physical capacity in patient’s prior allo-HCT. In this multicentre single arm pilot study, a supervised exercise program was performed twice weekly for 4–12 weeks prior allo-HCT, depending on the individual time remaining. Outcomes were feasibility (recruitment, adherence, safety), physical capacity (cardiorespiratory fitness [VO2peak], muscle strength) and patient reported outcomes (physical functioning, fatigue). Thirty patients were intended, 16 could be included, and 14 completed post intervention assessment (75% male, 55 ± 11 years). The study was stopped early due to a low recruitment rate. Nine patients (64%) reached the initial minimum planned number of eight exercise sessions. Individual adherence was high with 92% for HIIT and 85% for RE. 87% of all performed exercise sessions were completed without complaints and VO2peak increased significantly from 20.4 to 23.4 ml/kg/min. The low recruitment rate suggests that initiation of the intervention concept immediately before allo-HCT is feasible only in a small number of patients. In particular, the timeframe directly prior allo-HCT seems too short for exercise interventions, although the exercise program was designed to improve outcomes in a very short time frame. HIIT and RE were feasible, effective and well accepted by the included patients.
Early diagnosis of oral cancer using a hybrid arrangement of deep belief networkand combined group teaching algorithm
Authors: Wang Wenjing , Liu Yi , Wu Jianan
Published: December 2023

Oral cancer can occur in different parts of the mouth, including the lips, palate, gums, and inside the cheeks. If not treated in time, it can be life-threatening. Incidentally, using CAD-based diagnosis systems can be so helpful for early detection of this disease and curing it. In this study, a new deep learning-based methodology has been proposed for optimal oral cancer diagnosis from the images. In this method, after some preprocessing steps, a new deep belief network (DBN) has been proposed as the main part of the diagnosis system. The main contribution of the proposed DBN is its combination with a developed version of a metaheuristic technique, known as the Combined Group Teaching Optimization algorithm to provide an efficient system of diagnosis. The presented method is then implemented in the “Oral Cancer (Lips and Tongue) images dataset” and a comparison is done between the results and other methods, including ANN, Bayesian, CNN, GSO-NN, and End-to-End NN to show the efficacy of the techniques. The results showed that the DBN-CGTO method achieved a precision rate of 97.71%, sensitivity rate of 92.37%, the Matthews Correlation Coefficient of 94.65%, and 94.65% F1 score, which signifies its ability as the highest efficiency among the others to accurately classify positive samples while remaining the independent correct classification of negative samples.
Database screening as a strategy to identify endogenous candidate metabolites to probe and assess mitochondrial drug toxicity
Authors: De la Rosa Mery Vet George , Patel Dipali , McCann Marc R. , Stringer Kathleen A. , Rosania Gus R.
Published: December 2023

Adverse drug reactions (ADRs) are considered an inherent risk of medication use, and some ADRs have been associated with off-target drug interactions with mitochondria. Metabolites that reflect mitochondrial function may help identify patients at risk of mitochondrial toxicity. We employed a database strategy to identify candidate mitochondrial metabolites that could be clinically useful to identify individuals at increased risk of mitochondrial-related ADRs. This led to l-carnitine being identified as the candidate mitochondrial metabolite. l-carnitine, its acetylated metabolite, acetylcarnitine and other acylcarnitines are mitochondrial biomarkers used to detect inborn errors of metabolism. We hypothesized that changes in l-carnitine disposition, induced by a “challenge test” of intravenous l-carnitine, could identify mitochondrial-related ADRs by provoking variation in l-carnitine and/or acetylcarnitine blood levels. To test this hypothesis, we induced mitochondrial drug toxicity with clofazimine (CFZ) in a mouse model. Following CFZ treatment, mice received an l-carnitine “challenge test”. CFZ-induced changes in weight were consistent with previous work and reflect CFZ-induced catabolism. l-carnitine induced differences in whole blood acetylcarnitine concentrations in a manner that was dependent on CFZ treatment. This supports the usefulness of a database strategy for the discovery of candidate metabolite biomarkers of drug toxicity and substantiates the potential of the l-carnitine “challenge test” as a “probe” to identify drug-related toxicological manifestations.
Automatic diagnosis of true proximity between the mandibular canal and the third molar on panoramic radiographs using deep learning
Authors: Jeon Kug Jin , Choi Hanseung , Lee Chena , Han Sang-Sun
Published: December 2023

Evaluating the mandibular canal proximity is crucial for planning mandibular third molar extractions. Panoramic radiography is commonly used for radiological examinations before third molar extraction but has limitations in assessing the true contact relationship between the third molars and the mandibular canal. Therefore, the true relationship between the mandibular canal and molars can be determined only through additional cone-beam computed tomography (CBCT) imaging. In this study, we aimed to develop an automatic diagnosis method based on a deep learning model that can determine the true proximity between the mandibular canal and third molars using only panoramic radiographs. A total of 901 third molars shown on panoramic radiographs were examined with CBCT imaging to ascertain whether true proximity existed between the mandibular canal and the third molar by two radiologists (450 molars: true contact, 451 molars: true non-contact). Three deep learning models (RetinaNet, YOLOv3, and EfficientDet) were developed, with performance metrics of accuracy, sensitivity, and specificity. EfficientDet showed the highest performance, with an accuracy of 78.65%, sensitivity of 82.02%, and specificity of 75.28%. The proposed deep learning method can be helpful when clinicians must evaluate the proximity of the mandibular canal and a third molar using only panoramic radiographs without CBCT.
Analysis of geometric morphometrics and molecular phylogeny for Anopheles species in the Republic of Korea
Authors: Jeon Jiseung , Kim Heung Chul , Klein Terry A. , Choi Kwang Shik
Published: December 2023

Human malaria, transmitted byAnophelesmosquitoes, is the most predominant mosquito-borne disease that is responsible for hundreds of thousands of deaths worldwide each year. In the Republic of Korea (ROK), there are currently several hundred malaria cases annually, mostly near the demilitarized zone (DMZ). Eight species ofAnophelesmosquitoes are currently known to be present in the ROK. Similar to other major malaria vectors in Africa and India, it is very challenging to morphologically differentiateAnophelesmosquitoes in the ROK due to their extremely similar morphology. In this study, wing geometric morphometrics (WGM) were used to differentiate the eightAnophelesspecies collected at six locations near the DMZ, Seoul and Pyeongtaek from April–October 2021. Phylogenetic analysis was also performed using cytochromecoxidase subunit 1 (COI), internal transcribed spacer 2 (ITS2), and tyrosine hydroxylase (TH) genes for comparison with WGM analysis and to infer evolutionary relationships. The results of cross-validation (overall accuracy = 74.8%) demonstrated that species identification using WGM alone was not possible with a high accuracy for all eight species. While phylogenetic analyses based on theCOIregion could not clearly distinguish some species, the analysis based on ITS2 andTHwas more useful for resolving the phylogenetic correlation of the eight species. Our results may improveAnophelesspecies identification strategies for effective identification and control of malaria vectors in the ROK.
AI-based diagnosis of nuclear cataract from slit-lamp videos
Authors: Shimizu Eisuke , Tanji Makoto , Nakayama Shintato , Ishikawa Toshiki , Agata Naomichi , Yokoiwa Ryota , Nishimura Hiroki , Khemlani Rohan Jeetendra , Sato Shinri , Hanyuda Akiko , Sato Yasunori
Published: December 2023

In ophthalmology, the availability of many fundus photographs and optical coherence tomography images has spurred consideration of using artificial intelligence (AI) for diagnosing retinal and optic nerve disorders. However, AI application for diagnosing anterior segment eye conditions remains unfeasible due to limited standardized images and analysis models. We addressed this limitation by augmenting the quantity of standardized optical images using a video-recordable slit-lamp device. We then investigated whether our proposed machine learning (ML) AI algorithm could accurately diagnose cataracts from videos recorded with this device. We collected 206,574 cataract frames from 1812 cataract eye videos. Ophthalmologists graded the nuclear cataracts (NUCs) using the cataract grading scale of the World Health Organization. These gradings were used to train and validate an ML algorithm. A validation dataset was used to compare the NUC diagnosis and grading of AI and ophthalmologists. The results of individual cataract gradings were: NUC 0: area under the curve (AUC) = 0.967; NUC 1: AUC = 0.928; NUC 2: AUC = 0.923; and NUC 3: AUC = 0.949. Our ML-based cataract diagnostic model achieved performance comparable to a conventional device, presenting a promising and accurate auto diagnostic AI tool.
Improving the efficiency of using multivalued logic tools: application of algebraic rings
Authors: Suleimenov Ibragim E. , Vitulyova Yelizaveta S. , Kabdushev Sherniyaz B. , Bakirov Akhat S.
Published: December 2023

It is shown that in order to increase the efficiency of using methods of abstract algebra in modern information technologies, it is important to establish an explicit connection between operations corresponding to various varieties of multivalued logics and algebraic operations. For multivalued logics, the number of variables in which is equal to a prime number, such a connection is naturally established through explicit algebraic expressions in Galois fields. It is possible to define an algebraic δ-function, which allows you to reduce any truth table to an algebraic expression, for the case when the number of values accepted by a multivalued logic variable is equal to an integer power of a prime number. In this paper, we show that the algebraic δ-function can also be defined for the case when the number of values taken by a multivalued logic variable is p − 1, where p is a prime number. This function also allows to reduce logical operations to algebraic expressions. Specific examples of the constructiveness of the proposed approach are presented, as well as electronic circuits that experimentally prove its adequacy.
Linking microbiome and stress hormone responses in wild tropical treefrogs across continuous and fragmented forests
Authors: Neely Wesley J. , Martins Renato A. , Mendonça da Silva Camila M. , Ferreira da Silva Tainá , Fleck Lucas E. , Whetstone Ross D. , Woodhams Douglas C. , Cook W. Harrison , Prist Paula R. , Valiati Victor H. , Greenspan Sasha E. , Tozetti Alexandro M. , Earley Ryan L. , Becker C. Guilherme
Published: December 2023

The amphibian skin microbiome is an important component of anti-pathogen defense, but the impact of environmental change on the link between microbiome composition and host stress remains unclear. In this study, we used radiotelemetry and host translocation to track microbiome composition and function, pathogen infection, and host stress over time across natural movement paths for the forest-associated treefrog, Boana faber. We found a negative correlation between cortisol levels and putative microbiome function for frogs translocated to forest fragments, indicating strong integration of host stress response and anti-pathogen potential of the microbiome. Additionally, we observed a capacity for resilience (resistance to structural change and functional loss) in the amphibian skin microbiome, with maintenance of putative pathogen-inhibitory function despite major temporal shifts in microbiome composition. Although microbiome community composition did not return to baseline during the study period, the rate of microbiome change indicated that forest fragmentation had more pronounced effects on microbiome composition than translocation alone. Our findings reveal associations between stress hormones and host microbiome defenses, with implications for resilience of amphibians and their associated microbes facing accelerated tropical deforestation.