bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre and post diagnostic dementia care in four Scottish prisons
Authors: MacRae Rhoda , Chalmers Natalie , Tolson Debbie , Taylor James , Anderson Kirstin , Thompson Lindsay , Russ Tom
Published: May 2024

Background and purpose: The number of older people in prisons is increasing across the globe. Many have poor physical and mental health, higher prevalence of head injury, cognitive impairment and dementia than found in community populations. Meeting the complex needs of this vulnerable group has become an increasing concern for prison and prison healthcare services. This multi method qualitative study investigated how men with diagnosed or suspected dementia were identified, assessed, and cared for in Scottish prisons. The lived experience of individuals being assessed for or diagnosed with dementia within four prisons was also explored. This evidence was used to collaboratively propose principles for dementia care in prison and present the resultant co-designed care pathway.
Results: At the time of data collection almost all the men known to have a dementia diagnosis or suspected dementia had complex health and social care needs, and some were living with advanced dementia. Prison healthcare staff reported taking a ‘case by case’ approach to their pre- and post-diagnostic care. Meeting these prisoner’s needs was complicated by the absence of organisational leads for care of older adults or people with dementia and there was no pathway or model in place to guide staff. Prison healthcare teams often had difficulty accessing specialist community services to support diagnosis. There was a lack of dementia education and knowledge about how to provide pre and post diagnostic dementia care in this setting amongst staff. The findings arising from this research have informed the co-production of two important evidence informed innovations namely a Model of Care and a Care Pathway.
Conclusion: This research adds insights critical to understanding the adequacy of current approaches to meeting dementia related needs within the prison setting. To our knowledge this paper offers the first co-produced evidence informed pre- and post- diagnostic dementia care pathway and model of care for use in prisons. These could serve as tools for change that could enable prison healthcare staff to deliver the right care, at the right time, by the right people, and provide an opportunity to assess risk and plan care for the future.
Low Dose Rituximab and Calcineurin Inhibitor Combination as an Effective Treatment Strategy in Relapsed Primary Membranous Nephropathy
Authors: Yanık Ahmet Mert , Berke İlay , Aykent Mahmut Başar , Velioğlu Arzu , Aşıcıoğlu Ebru , Tuğcu Murat , Barutçu Dilek , Tuğlular Zübeyde Serhan , Koç Mehmet , Arıkan İzzet Hakkı
Published: May 2024

Purpose:In primary membranous nephropathy (PMN), treatment includes tailored immunosuppressive protocols to reduce renal progression risks, with relapse being a common challenge. Nevertheless, the existing body of literature on utilizing Rituximab (RTX) and calcineurin inhibitors (CNIs) in such cases is limited. We aimed to document the outcomes associated with the combined use of low-dose RTX and CNIs in the treatment of relapsed PMN patients with a moderate to high risk.
Methods: In this retrospective study, 22 relapsed PMN patients (22.7% female, average age 51.2 ± 12 years) were included. At the time of diagnosis, 27% (n=6) were identified as high-risk and 73% (n=16) as moderate-risk. The Patients were treated with two doses of 500 mg RTX administered 15 days apart. Low-dose CNI was started (n=2) or maintained (n=20) combined with RTX therapy.
Results: Mean post-treatment follow-up period was 46.9 ± 11.9 months. Initial mean proteinuria was 5.9 ± 3 g/day, decreasing to 2.1 ± 2.5 g/day by 12 months and to 2 ± 2.4 g/day by 24 months post-treatment. All achieved remission following treatment. Of these, 41% and 59% attained complete (CR) and partial remission (PR), respectively. The median time to remission was 6.68 months, with an average duration of sustained remission noted at 26.5 months. Sixteen patients (72.7%) experienced relapse, necessitating additional RTX doses after 20.1 (50±4) months. Serious adverse events were documented in 3 patients (13.6%).
Conclusion: Our results suggest that the combination of low-dose RTX and CNI could be a viable and safe treatment option for relapsed PMN patients with a moderate to high risk. The synergistic impact of CNI and RTX may augment treatment effectiveness, enabling the use of reduced RTX dosages. This approach might be a effective and safe treatment protocols.
NPT100-18A rescues mitochondrial oxidative stress and neuronal loss in human iPSC-based Parkinson's model
Authors: Alecu Julian E. , Sigutova Veronika , Brazdis Razvan-Marius , Lörentz Sandra , Bogionko Marios , Nursaitova Anara , Regensburger Martin , Roybon Laurent , Galler Kerstin M. , Wrasidlo Wolfgang , Winner Beate , Prots Iryna
Published: May 2024

Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections result in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS). These factors have been shown to adversely impact αSyn aggregation. Reciprocally, αSyn aggregates, in particular oligomers, can impair mitochondrial functions and exacerbate OS. Recent drug-discovery studies have identified a series of small molecules including NPT100-18A, which reduce αSyn oligomerization by preventing misfolding and dimerization. NPT100-18A and structurally similar compounds (such as NPT200-11/UCB0599, currently being assessed in clinical studies) point towards a promising new approach for disease-modification.
Methods Induced pluripotent stem cell (iPSC)-derived mDANs from PD patients with a monoallelic SNCA locus duplication and unaffected controls were treated with NPT100-18A. αSyn aggregation was evaluated biochemically and reactive oxygen species (ROS) levels were assessed in living mDANs using fluorescent dyes. Adenosine triphosphate (ATP) concentrations were measured using a luminescence-based assay and neuronal cell death was evaluated by immunocytochemistry.
Results Compared to controls, patient-derived mDANs exhibited increased αSyn aggregation, higher overall ROS levels, reduced ATP concentrations, and increased neuronal cell death. NPT100-18A-treatment rescued neuronal cell death to control levels and importantly attenuated mitochondrial oxidative stress in a compartment-specific manner.
Conclusions Our findings demonstrate that NPT100-18A limits αSyn aggregation and associated neurodegeneration in a human in vitro model of PD. In addition, we provide a first mechanistic insight into how a compartment-specific antioxidant effect in mitochondria might contribute to the neuroprotective effects of NPT100-18A.
Patterns and determinants of imported malaria near Argentina-Bolivia border 1977 - 2010
Authors: Berlin Erica , Juri María J. Dantur , Zaidenberg Mario , Duque Paul L. , Madariaga Horacio , Navarro Juan C. , Castro Marcia C.
Published: May 2024

In the Americas, the number of malaria cases has decreased dramatically in the past 15 years, and malaria elimination is now in sight for many countries. Argentina is currently free of autochthonous malaria transmission. Until 2011, cases of malaria were concentrated in the Northwest near the border with Bolivia, a country that continues to have malaria transmission. Orán department, in Salta province, had particularly high transmission near a main road that is a pathway for migration from Bolivia. The purpose of this research was to identify which factors best explain the extent and timing of changes in the proportion of malaria cases in this area that were locally transmitted versus acquired in another country. Combining information from routinely collected case investigations, epidemiological surveillance data, and satellite imagery, we used a logistic model and a multilevel model of change to identify how demographic and place-level variables influence the proportion of malaria cases that were imported over time. The findings showed that the proportion of cases that were imported varied significantly over time and that the variation could be explained by the demographic characteristics of cases. In particular, there was a change in transmission patterns after a cross-border intervention was launched in 1996. In addition, proximity to mosquitos was an important determinant of local transmission. Based on lessons learned from the characterization of transmission trends, policies were proposed for preventing malaria reintroduction in Argentina.
RV Myocardial Work Reserve as Clinical Improvement Predictor in HFrEF Patients after TEER-A Pilot Study
Authors: Wang Yi , Shu Qinglan , Liu Yi , Lu Cong , Xu Yun , Zhou Yi , Zhang Qingfeng , Ye Luwei , Meng Qingguo , Wang Sijia , Yao Yuan , Lin Xinyi , Zeng Jie
Published: May 2024

Backgrounds:
It remains uncertain which kind of heart failure with reduced ejection fraction (HFrEF) patients would benefit the most from transcatheter edge-to-edge repair (TEER).
Objectives
We aim to investigate the relationship between right ventricular function, as assessed by pressure-strain loops (PSL), and post-TEER clinical improvement.
Methods
A total of 48 HFrEF patients (68 ± 15 yrs) with moderate-to-severe or severe SMR were enrolled for TEER. Impaired health status (Kansas City Cardiomyopathy Questionnaire Overall Summary Score [KCCQ-OS]) and exercise capacity (6-min walk distance [6MWD]) were evaluated at baseline and during 1-year follow up. Before and right after TEER, myocardial work (MW) metrics were non-invasively evaluated, including global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE).
Results
RV GLS, RVGWI, RVGCW, RVGWE were significantly increased after MitraClip treatment (-9.7 ± 3.8%, 452.4 ± 112.5 mmHg%, 596.3 ± 127.5 mmHg% and 85.7 ± 15.6% before vs -12.5 ± 3.5%, 589.4 ± 119.6 mmHg%, 778.8 ± 135.3 mmHg% and 91.2 ± 22.4% after MitraClip treatment, p = 0.025, 0.030, 0.025 and 0.037, respectively). The Kaplan-Meier estimates for survival, freedom from HF hospitalization at 12 months were 95.8% and 89.1%. On multivariable linear regression analysis, RVGWI and RVGCW immediate change was independently associated with KCCQ-OS (△RVGWI: 𝛃 = 0.40, P < 0.001; △RVGCW: 𝛃 = 0.39, P = 0.003), RVGWI, RVGCW and RVGLS immediate change were independently associated with 6MWD improvement (△RVGWI: 𝛃 = 0.31, P = 0.029; △RVGCW: 𝛃 = 0.30, P = 0.039; △RVGLS: 𝛃 = 0.35, P = 0.041).
Conclusion
RVMW was significantly increased after MitraClip treatment. And RV reserve function is an important predictor of clinical improvement in HFrEF patients with TEER.
Recovering water from fossil fuel to break the constraints of sustainable development of resource-based cities
Authors: Gao Dan , Li Zhaohao , Zhi Tianyi , Liu Huan , Zhang Heng , Chen Haiping , Liu Jizhen
Published: May 2024

Adequate water resources are the key to the urban development. Unlike other water-scarce cities, the cities in Northwest China are rich in fossil fuels. In view of this, exploring the feasibility of recovering water from fossil energy in the industrial application is a novel idea to relieve water resources stress. Taking 49 cities in Northwest China as an example, we propose three specific water recovering scenarios based on the urban development status and the fossil energy consumption. The results show that the total amount of recovered water of northwest cities is expected to reach 1535.61 megatons, accounting for 39.69% of the total industrial water. Furthermore, according to the characteristics of the urban development in Northwest China, we put forward a novel evaluation method of economic benefits brought by water recovering. For the northwest cities, there is a serious imbalance among the economic investment, the fossil energy, the industrial development, the human resources and the water resources, and the shortage of water resources makes it difficult to apply a large number of idle resources to the urban development. We focus on analyzing the contribution of water recovering to the urban GDP growth, and assesse the type of industrial development in the each city. The results show that the recovered water can effectively promote the urban economic development, and the 49 cities are expected to increase their GDP by 1579.38 billion yuan due to water recovering. The method of water recovery from fossil energy is expected to improve the ecological environment of the cities in Northwest China, and it is expected to create three commercial circles in the east, central and western regions with Xianyang, Wuwei and Turpan as the cores. This research has important implications for the sustainable development of other water-scarce cities around the world.
Trends in Ophthalmic Surgery for The Very Older Patients in Japan Using the National Claims Database
Authors: Kabata Yoshiaki , Terauchi Ryo , Nakano Tadashi
Published: May 2024

Background
To investigate the trends in the number of ophthalmic surgeries performed in the very older patients in Japan using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open data.
Methods
We used accumulated NDB data from fiscal year (FY) 2017 to 2021. Glaucoma surgery was defined as the surgical code K268. Vitrectomy is the sum of the total numbers from K272 to K281. Cataract surgery was defined as K282. In particular, we calculated the growth rate of the Japanese population aged 85 to 90 and 90 years and over in 2017 and 2021, and the growth rate of the number of surgeries in FY2017 and FY2021.
Results
Japan's population growth rate from 2017 to 2021 was 14% (aged 85–90) and 24% (aged 90 <), and the growth rate in the number of surgeries in glaucoma surgeries, vitrectomy, and cataract surgery from FY2017 to FY2021 was 45%, 16%, and 38% (aged 85–90), and 50%, 28%, and 46% (aged 90 <), in all cases exceeding population growth rates. Among glaucoma surgeries, outflow reconstruction increased significantly; the growth rate was 166% (aged 85–90) and 60% (aged 90 <).
Conclusion
Cataract, glaucoma, and vitreous surgeries showed an increasing trend, and a transient decrease was observed due to COVID–19 in FY2020 in the very older patients in Japan. Among glaucoma surgeries, the number of outflow reconstruction has increased significantly in 85–90 years old.
A family of Dai-Liao conjugate gradient methods with strong convergence for Image restoration and Machine learning
Authors: Jiang Xianzhen , Sun Guoqing , Jian Jinbao
Published: May 2024

Conjugate gradient method is one of the most effective schemes to deal with large-scale optimization problems. In this study, three classes of parameters for the Dai-Liao conjugate condition are provided to be chosen, and thus a new Dai-Liao conjugate parameter is derived. Making a truncation for the conjugate parameter and introducing a restart procedure into the search direction, a family of improved Dai-Liao conjugate gradient methods is proposed. It is sufficient descent at each iteration without depending on the choice of the line search criterion. Under usual assumptions, and using the weak Wolfe line search criterion to yield its steplength, its strong convergence is proved. Finally, choosing a specific algorithm from this family to solve large-scale unconstrained optimization problems, image restorations and machine learning, the corresponding numerical results show that the new algorithm is promising.
Mathematics Subject Classification (2020) 65K05 · 90C52 · 90C53 · 90C56
Barriers and enablers to utilisation of postpartum long-acting reversible contraception in Eastern Uganda: a qualitative study
Authors: Kamwesigye Assen , Amanya Daphine , Nambozo Brendah , Epuitai Joshua , Nahurira Doreck , Wani Solomon , Nafula Patience A M , Oguttu Faith , Wadinda Joshua , Nantale Ritah , Napyo Agnes , Wandabwa Julius N , Mukunya David , Musaba Milton W , Willcox Merlin
Published: May 2024

Introduction
In Uganda, women experience multiple missed opportunities to receive counselling for postpartum family planning services along the continuum of maternity care. We explored the enablers and barriers to utilisation of postpartum long-acting reversible contraceptives in Eastern Uganda.
Methods
We conducted a qualitative study in two districts of Eastern Uganda. We had 39 interviews. We conducted 20 in-depth interviews and three focus group discussions with postpartum women, male partners, health workers, and village health team memberss. Our study was grounded in the COM-B framework, and the transcripts were analysed thematically.
Results
The use of immediate postpartum long-acting reversible contraception (LARC) was majorly hindered by both incapabilities and limited opportunites in the health system and patient factors. System factors included lack of healthcare provider-initiated counselling for postpartum contraception, overburdened healthcare workers, and shortage of Postpartum Family Planning commodities and sundries. Patient factors included limited knowledge (lack of awareness for postpartum contraception), misconceptions (perceived body fragility, need to fully recover and for menses to resume after delivery), fear of side effects, men had fear of infidelity, lack of agency to ask for health education and poor health seeking behaviours. The enablers for immediate postpartum LARC included positive attitudes towards contraception, preference for contraceptive implants over intra uterine devices (IUD) at the 6-week postpartum period, resumption of sex and menses, partner support, and perceived effectiveness of postpartum contraception. Participants thought that sensitization about LARC through health education and outreach visits, male involvement through ANC appointments and male village health teams, and switching between family planning methods could improve uptake of immediate postpartum LARC.
Conclusion
Inadequate knowledge and skills on postpartum family planning services(PPFPs) and lack of health education by health workers and misconceptions with poor partner support majorly led to low utilisation of postpartum family planning services in this setting. Scaling up effective, low cost and innovative ways to provide PPFP services such as video counselling may improve the use of immediate postpartum LARCs. As well as actively promoting the provision of intergrated services along the continuum of maternity care.
Vaccine Prevention of Pneumococcal Infection Among Patients With Chronic Obstructive Pulmonary Disease and Coronary Heart Disease –- A 10-year Horizon of Effectiveness
Authors: Ignatova Galina L. , Avdeev Sergey N. , Antonov Vladimir N. , Blinova Elena V. , Osikov Mikhail V.
Published: May 2024

Summary: The article provides an analysis of the clinical effectiveness of the use of the 13-valent conjugate pneumococcal vaccine (PCV13) among patients with comorbidity of chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD).
The main objective of this study was to assess the effectiveness of PCV13 on the incidence of community-acquired pneumonia (CAP), as well as the impact on the survival rates of patients with COPD and CHD over fa 10-year period.
Materials and methods: 500 male patients with COPD and CHD were included in the study. The primary endpoint was the incidence of CAP during 10 years of follow-up. Secondary endpoints were any-cause of mortality, exacerbations, hospitalizations during 10 years of follow-up and also the dynamics of dyspnea according to mMRC, forced expiratory volume in the first second (FEV1), dynamics of changes in 6MWD, dynamics of changes in functional class of angina pectoris (FC). The 13-valent conjugated pneumococcal vaccine (Prevenar 13) has utilised for immunization.
Results and conclusions: PСV13 vaccination has a significant impact on patient survival, at least during the 10-year follow-up period. The utilising of the 13-valent conjugated pneumococcal vaccine leads to a significant reduction of the high morbidity for CAP among patients with COPD, as well as with COPD and CHD. Vaccination leads to the stabilization of the main clinical and functional parameters, including during a 10-year perspective. Recommendations to include pneumococcal vaccines in clinical guidelines and immunization programs should be mandatory and prioritized.
Highly Sensitive Detection of Kojic Acid in Food Samples Using Fluorescent Carbon Dots derived from Pomegranate peel
Authors: Omar Omnia , Saad Ahmed , Ghali Mohsen
Published: May 2024

We report on this work development of a highly responsive optical sensor for the detection of Kojic acid (KA) using fluorescent Carbon dots (CDs) derived from pomegranate peel. The CDs were extensively characterized to validate their structural properties and intrinsic fluorescence. Utilizing the fluorescence of synthesized CDs, the optical sensor based on the CDs fluorescence quenching. Sensor was developed for the rapid and sensitive detection of KA in food products, such as vinegar and soy sauce. The sensor exhibited high performance in a wide KA concentration range of 120–1200 µM with a limit of detection LOD reached 30 µM, showcasing its potential for practical applications in assessing food quality and safety.
Application of Infrared Thermography in the Detection of Pathological Manifestations of the Stone Chalet in the City of Quixadá, Brazil
Authors: BEZERRA Macgyver Viana , SANTOS Anny Caroline Nobre , SILVA Ítalo Costa , RODRIGUES Bruno Noronha
Published: May 2024

Historical-cultural heritage is a testimony to the formation of people and should be preserved to maintain their identity over time. Thus, historical buildings are part of this heritage and should be valued and kept in exemplary conservation, use, and safety conditions. In this regard, the importance of Diagnostic Engineering in reducing constructive anomalies and associated costs of technical assistance is evident. This field utilizes essential tools, such as visual inspection, which evaluates the technical conditions for the use and maintenance of buildings. Additionally, Non-Destructive Testing (NDT), such as infrared thermography (IRT), is a powerful tool for non-invasive detection of constructive flaws in historical buildings. In this context, the objective of this study was to conduct visual inspections and identify pathological manifestations in a historical building in the city of Quixadá, Brazil. This is applied research with objectives fitting descriptive and exploratory research, a qualitative-quantitative approach, and a procedure classified as a case study. Thus, on-site visual inspections of the building were carried out, the pathological manifestations were classified according to the parameters of the GUT Matrix and Delphi Method, and an analysis of manifestations related to humidity was conducted through IRT. It was concluded that the historic building is in a critical state of conditions of use, representing risks to the safety of users, and is prone to accidents and structural collapses. As a contribution, this research represents a robust analysis based on Diagnostic Engineering and the use of IRT to analyze pathological manifestations in historical-cultural buildings.
Stability estimation of Mount St. Helens using Scoops3D and ensemble learning paradigms
Authors: Kumar Sumit , Kumar Sudeep , Suman Subodh Kumar , Kumar Amit , Bardhan Abidhan
Published: May 2024

This research investigates the application of ensemble-based computational paradigms to estimate the stability of Mount St. Helens. Scoops3D was initially utilized for conducting slope stability investigation, followed by computational modelling of the factor of safety (FOS) employing various influencing parameters. Four base models including AdaBoost regressor, decision tree regressor, extra tree regressor, and gradient boosting regressor, and a bagging-based ensemble learning (BG-ENSM) framework, were used for this purpose. In both seismic and non-seismic conditions, the effect of pore-pressure ratio (ru) on the stability of Mount St. Helens was investigated in three different combinations (i.e., Cases-1, 2, and 3) with ru = 0, ru = 0.3, and ru = 0 and 0.3. Post computational modelling, the outcomes of the implemented paradigms were evaluated based on several indicators. Experimental outcomes exhibit that the proposed BG-ENSM framework achieved the most desired estimation of FOS with R2 of 0.9968, 0.9959, and 0.9985 against Cases-1, 2, and 3, respectively. Based on the overall results and the outcomes of parametric study, the employed BG-ENSM framework can be considered as a viable tool for stability estimation of Mount St. Helens considering the effect of ru in seismic and non-seismic conditions.
Knowledge of Neonatal Danger Signs and Associated Factors Among Husbands with Neonate at Bale Zone, Southeast Ethiopia
Authors: umer Meimuna Umer Muhammed , Fikadu Genet Fikadu Haile , Esmael Adem Esmael Roba , Tadesse Samrawit Tadesse Damena
Published: May 2024

Background
Neonatal mortality has remained high in Ethiopia despite different efforts being undertaken to reduce this negative trend. Early detection of neonatal illnesses is an important step toward improving newborn survival. Knowledge of husbands towards neonatal danger signs especially in developing countries, like Ethiopians is very important, as mothers' access to health care is largely affected by their husbands' decision-making. However, there is limited information about the knowledge of husbands on neonatal danger signs and associated factors in the study area. This study aims to assess husbands’ knowledge on neonatal danger signs, and associated factors.
Methods
Community-based cross-sectional study conducted at Bale zone south-east Ethiopia in 2023 among 408 respondents selected by using simple random sampling method. Data were collected using interviewer administered questionnaire. Both bivariable and multivariable logistic regression were utilized.
Result
The study reveals that husbands good knowledge of neonatal danger signs was 44% (95% CI: 0.39–0.49). Regarding the factors; husbands level of education (AOR = 2.18, (95% CI; [1.05, 4.54]), and having information on neonatal danger sign (AOR = 6.91, 95% CI; [3.58, 13.35]) were factors significantly associated with husbands’ knowledge on neonatal danger signs.
Conclusion
The proportion of Husbands’ knowledge on neonatal danger sign was low. Husbands’ level of education and having information on neonatal danger signs were factors significantly associated with husbands’ knowledge on neonatal danger sign. Hence, the best way to address the health of newborns is to raise awareness and encourage husbands to actively participate in the process of obtaining medical attention.
Detection and characterization of colorectal cancer by autofluorescence lifetime imaging: a preliminary study on surgical specimens
Authors: Herrando Alberto Ignacio , Fernández Laura M. , Azevedo José , Vieira Pedro , Domingos Hugo , Galzerano Antonio , Shcheslavskiy Vladislav , Heald Richard J. , Parvaiz Amjad , Silva Pedro Garcia da , Castillo-Martin Mireia , Lagarto João L.
Published: May 2024

Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, driving a quest for comprehensive characterization methods. We report a characterization of the ex vivo autofluorescence lifetime fingerprint of colorectal tissues obtained from 73 patients that underwent surgical resection. We specifically target the autofluorescence characteristics of collagens, reduced nicotine adenine (phosphate) dinucleotide (NAD(P)H), and flavins employing a fiber-based dual excitation (375 nm and 445 nm) optical imaging system. Autofluorescence-derived parameters obtained from normal tissues, adenomatous lesions, and adenocarcinomas were analyzed considering the underlying clinicopathological features. Our results indicate that differences between tissues are primarily driven by collagen and flavins autofluorescence parameters. We also report changes in the autofluorescence parameters associated with NAD(P)H that we tentatively attribute to intratumoral heterogeneity, potentially associated to the presence of distinct metabolic subpopulations. Changes in autofluorescence signatures of tumors were also observed with lymphatic and venous invasion, differentiation grade, and microsatellite instability. Finally, we characterized the impact of radiative treatment in the autofluorescence fingerprints of rectal tissues and observed a generalized increase in the mean lifetime of radiated tumors, which is suggestive of altered metabolism and structural remodeling. Overall, our preliminary findings indicate that multiparametric autofluorescence lifetime measurements have the potential to significantly enhance clinical decision-making in CRC, spanning from initial diagnosis to ongoing management. We believe that our results will provide a foundational framework for future investigations to further understand and combat CRC exploiting autofluorescence measurements.
Association of sleep traits, physical activity and leisure sedentary behavior with women’s reproductive health: a two-sample Mendelian randomization analysis
Authors: Zhang Jiaxin , Wang Tao , Yang Pusheng , Miao Yaxin , Ge Beilei , Sun Jing
Published: May 2024

Background: Living habits affect women's endocrine and fertility over time with aging and in certain circumstances, according to which we can promote women's reproductive health by adjusting living habits.
Methods: We utilized two-sampleMendelian randomization (TSMR) analysis with summary datasets from genome-wide association study (GWAS) to investigate the causal relationship between sleep traits, leisure sedentary behavior, physical activity and women’s reproductive health-related traits. Exposure genetic instruments were used as variants significantly related to traits. The inverse-variance weighted (IVW) method was used as the main analysis approach, and we also performed MR-Egger and weighted median to supplement the sensitivity test. Then, the horizontal pleiotropy was detected by using MRE intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran’s Q statistics by IVW and MR-Egger.
Results: We found evidence that insomnia showed a significant inverse causal association with the endometriosis [OR (95% CI) IVW = 1.80 (1.16, 2.80), P = 0.009], and with the abnormal menstruation [OR (95% CI) IVW = 2.37 (1.34, 4.20), P = 0.003]. What else the sleep duration has the negative relation menopause age (beta IVW = −0.034, P = 0.001), the long sleep duration might be the protective factor of endometriosis [OR (95% CI) IVW = 0.07 (0.01, 0.72), P = 0.024], strenuous sports were also negatively correlated with the female infertility[OR (95% CI) IVW = 0.10 (0.02, 0.68), P = 0.019]. In sensitivity analysis, we observed no sign of horizontal pleiotropy or heterogeneity.
Conclusion: Our finding suggested insomnia was an adverse factor of endometriosis and abnormal menstruation, long sleep duration was a protective factor with endometriosis. Therefore, adequate sleep and regular schedule might decrease the risk of endometriosis and abnormal menstruation to guarantee the women reproductive health.
Medical Laboratory Technology (MLT) study criteria, and training drawbacks in Pakistani institutions a web-based survey
Authors: Shoukani Hussan Ibne , Kubra Khudija tul
Published: May 2024

Background
Medical Laboratory Technology (MLT) is an allied health profession, that performs diagnostic tests by using different tools and analyzes the biological samples for the diagnosis of diseases to monitor the patient's health, after that the physician decides his medical opinion based on lab investigation. Sometimes patients suffer from death or life conditions, at that time accurate lab investigations can facilitate the physician to make the best decision which can help to save the patient's life. This needs a well-settled teaching lab which should be attached to a teaching hospital, to produce qualified medical lab professionals.
Objective
This study aimed to define the required professional criteria for medical lab technology and the evolution of training drawbacks in Pakistani institutions.
Methods
Study data summarized from different verified sources such as institutional websites, course and training curriculums of MLT offering institutions. They were defined in different grades according to the fulfillment of professional requirements. Out of n = 185 institutions (offering MLT courses and degrees), only n = 18 (9.72%) are in A-Grade level institutes which are fulfilling all requirements of MLT qualification, n = 17 (9.18%) are situated in B-Grade, n = 84 (45.40%) are part of C-Grade, and n = 66(36.67%) ranked in D-Grade institutions.
Conclusion
Based on standard MLT qualification requirements this study showed that most institutions offering MLT without any proper job training facilitation of clinical lab departments, and no proper affiliation with any clinical teaching lab.
Rapid Resolution of Newly Formed Carotid Free-Floating Thrombus Through Anticoagulation Therapy
Authors: Xie Fuli , Liang Lili , Wang Yuzhou
Published: May 2024

Background
Carotid free-floating thrombus (CFFT) are rare but carry significant risks of ischemic strokes. While the predominant treatment modality typically involves vascular intervention, in this case study, we highlight the feasibility of alternative options, specifically short-term anticoagulation therapy guided by extensive radiological evaluation.
Case presentation:
We admitted a patient with acute ischemic stroke due to middle cerebral artery (MCA) occlusion, and the National Institutes of Health Stroke Score (NIHSS) was 15. The patient was satisfactorily revascularized by prompt intravenous alteplase thrombolysis, but a rare occurrence of carotid free-floating thrombus was found, which was the culprit for the occlusion of the MCA. Instead of surgical treatment, we performed extensive radiological evaluations for the thrombus, including high-resolution magnetic resonance and serial ultrasonic scans. The intramural thrombus is highly suspected to be newly formed, so we hypothesized it might respond to anticoagulant therapy. As expected, after short-term anticoagulant therapy of enoxaparin injection, CFFT significantly dissolved.
Conclusions
This case illustrates the efficacy of anticoagulation for newly formed CFFT and introduces a novel treatment protocol guided by extensive radiological evaluation.
Honokiol inhibits arsenic trioxide-induced cardiomyopathy by modulating ferroptosis via SIRT3 signaling pathway
Authors: Wei Qing-qing , Huang An-Liang , Liu Ning-xi , Zhang Yi-ran , Yang Fan
Published: May 2024

Background Our previous studies have confirmed that Honokiol exerts protective effect on cardiomyocytes and cardiac tissue against ATO-induced cardiotoxicity, which is attributed to inhibiting cardiomyocyte apoptosis via reduced oxidative stress.Objectives This research aimed to explore the entire mechanism by which Honokiol provides protection against arsenic trioxide-induced cardiotoxicity.Materials and methods 129S1/SvImJ male wild type (WT) mice and SIRT3-knockout (SIRT3−/−) mice with 129S1 background were applied to verify the pathway of Honokiol on myocardial toxicity of arsenic trioxide; MitoSox, carboxy-DCFDA and Amplex Red were used to detect oxidative stress; ferroptosis-associated markers (MDA, GSH, tissue iron, GPX4 and 4-HNE expression) were tested by test kit or immunohistochemistry; autophagic flux was analyzed by western blot.Results SIRT3 knockout abolishes protective effects of HKL in ATO-induced myocardial injury and hypertrophy; Honokiol protects myocardium from ATO-induced oxidative stress through SIRT3/SOD2 pathway; Honokiol inhibited ATO-induced ferroptosis via the SIRT3 pathway in myocardial tissues; Honokiol improve autophagic flux in cardiomyocytes exposed to ATO treatment. Autophagic flux plays a critical role in protective effect of Honokiol on ATO-induced ferroptosis. The present study confirmed that Honokiol inhibits oxidative stress injury and ferroptosis in cardiomyocytes by promoting the autophagic flux in cardiomyocytes through the activation of SIRT3.
Accurate, Scalable and Cross-platform Cell Identification for High-resolution Spatial Transcriptomics
Authors: Wang Chenfei , Sun Dongqing , Zhang Lele , Han Tong , Wu Qiu , Zhang Peng
Published: May 2024

Recent advances in spatial transcriptomics (ST) have brought unparalleled opportunities to unravel cellular diversity and cell-cell interactions within their spatial context. High-resolution ST techniques, including barcoding-based and imaging-based platforms, have achieved remarkable sub-cellular resolution. However, the precise segmentation of cells remains a significant challenge and hampers effective single-cell spatial analysis. Existing methods targeting specific techniques lack compatibility across different high-resolution ST platforms, and many of them cannot scale well to ST data with large fields of view. Here, we introduce Cellist, a novel multi-modal cell-segmentation method that synergistically combines image and expression information, enabling comprehensive investigations at the cell level. Employing Cellist on mouse brain Stereo-seq data, we showcased its superiority in yielding heightened within-cell homogeneity over existing methods. Furthermore, Cellist facilitated accurate spatial domain identification and cell-type annotation. Importantly, Cellist is suitable for various ST techniques including Seq-Scope, seqFISH+, STARmap, and 10x Xenium, exhibiting exceptional accuracy across diverse high-resolution ST platforms and biological systems, all while maintaining high computational efficiency. Finally, we applied Cellist to post-neoadjuvant immunotherapy non-small cell lung cancer (NSCLC) samples. Our analyses revealed the spatial heterogeneity of tumor clones and identified therapy response-related myeloid subtypes and structures. These findings highlight the immense potential of Cellist in enhancing the power of high-resolution ST techniques for characterizing the spatial organization of cells and unraveling intricate tissue architectures. Cellist is publicly available at https://github.com/wanglabtongji/Cellist.
Assessing Microbial Diversity in Open-Pit Mining: Metabarcoding Analysis of Soil and Pit Microbiota Across Operational and Restoration Stages
Authors: Reto Priscila Heredia , Rogel Rosita Castillo , Lucano Gabriela Palomino , Fallen Jean Louis , Vidaurre Karina Zapata , Febre Marisol Saavedra , Calle Gabriel Reyes , Rosell Juan Zingg , Perez Jimmy Lopez , Rosillo José Morán , Mialhe Eric , Diringer Benoit
Published: May 2024

Mine closure operations aim to restore the ecosystem close to its original state. Microorganisms are key components of the soil equilibrium and therefore essential to the restoration process. We used metabarcoding techniques to characterize the bacterial and fungal composition in pristine soils, stockpiled soils (topsoils), enriched stockpiled soils (technosoils), enriched and revegetated soils (revegetated technosoils), and visually distinct pits in an open pit gold mine. Comparative analysis indicated that pristine and topsoils exhibited the highest levels of richness, followed by technosoils and pits. Taxonomic analysis identified dominant microbes’ communities. For both bacteria and fungi, the dominant genera differed between pristine/topsoils and technosoils. Ecological similarity indices showed that topsoil microbial communities were separated from pristine soil. Revegetated technosoil showed more similarity to pristine/topsoil than freshly prepared technosoil, indicating an ongoing process of microbial restoration. All pit samples differed greatly in their microbial composition, with the presence of moisture and rock composition being the main axes of dissimilarity. It is concluded that the greater community complexity in soils is related to the availability of nutrients, physicochemical variations and the possibility of interaction with other microbes, while pits could be considered as extreme ecosystems that limit the growth of most microorganisms.
Thermostable fungal xylanase as a potential supplemental additive for commercial cellulase cocktails
Authors: Estevão Carlos Junior de Assis , Almeida Lucas Filipe , Arruda Luiz Vinícius de Souza , de Souza João Batista , Guimarães Valéria , Alfenas Rafael Ferreira , Maitan-Alfenas Gabriela
Published: May 2024

Enzymes are crucial in acquiring valuable biotechnological products, such as fermentable sugars, from alternative carbon sources. Lignocellulosic biomass, often derived from agro-industrial waste, serves as a renewable source for second-generation (2G) ethanol production employing cellulolytic and hemicellulolytic enzymes in the saccharification process, releasing glucose for alcoholic fermentation. Thus, there is a growing demand for novel catalysts that act in biomasses depolymerization, while remaining environmentally friendly. This study aimed to induce xylanase production by Ceratocystis fimbriata using barley, corn cob, and wheat bran as substrates. Additionally, the study evaluated the supplementation of a commercial cellulase cocktail with the partially purified fungal xylanase. The biomass substrates exhibited the highest xylanolytic activity after 8 days of cultivation, with barley yielding 21.20 U/mg. After partial purification through ion exchange chromatography, the xylanase produced in barley demonstrated activity of 67.34 U/mg, resulting in a purification factor of 3.2 and a yield of 56.9 %. The xylanase displayed optimal activity in the pH range of 2.0 to 8.0, retaining more than 50 % of its relative activity. Moreover, the enzyme displayed an optimal temperature of 55 °C and retained over 50 % of its activity after 72 hours at 50 °C. The supplemented Multifect® CL cocktail retained xylanase activity above 50 % for 72 hours, unlike the unsupplemented one. These findings unveiled the thermostability of C. fimbriata xylanase. Finally, the supplementation resulted in hydrolysis enhancement of pretreated sugarcane bagasse, leading to an increase of over 40 and 80 % in glucose and xylose production, respectively.
Structural basis for antibiotic transport and inhibition in PepT2, the mammalian proton-coupled peptide transporter.
Authors: Newstead Simon , Parker Joanne , Deme Justin , Lichtinger Simon , Kuteyi Gabriel , Biggin Philip , Lea Susan
Published: May 2024

The uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2). The mechanism by which SLC15 family transporters recognize and discriminate between different drug classes and dietary peptides remains unclear, hampering efforts to improve antibiotic pharmacokinetics through targeted drug design and delivery. Here, we present cryo-EM structures of the mammalian proton-coupled peptide transporter, PepT2, in complex with the widely used beta-lactam antibiotics cefadroxil, amoxicillin and cloxacillin. Our structures, combined with pharmacophore mapping, molecular dynamics simulations and biochemical assays, establish the mechanism of antibiotic recognition and the important role of protonation in drug binding and transport.
Exploring the host compound dynamics of 1,4-phenylene-bis(di-p-fluorophenylmethanol) in mixed pyridines
Authors: Barton Benita , Vorgers Jarryd A. , Hosten Eric C.
Published: May 2024

In this investigation, the wheel-and-axle host compound, 1,4-phenylene-bis(di-p-fluorophenylmethanol) H, was demonstrated to have inclusion ability for each of PYR, 2MP, 3MP and 4MP (1:1, 1:2, 1:2 and 1:2 were the H:G ratios). In the equimolar guest competition experiments, H was observed to have an overwhelming affinity for PYR and 4MP relative to 2MP and 3MP. In fact, selectivity coefficients calculated from the non-equimolar binary guest competition experiments suggested that this host compound would be an efficient candidate for the separation of all PYR/2MP mixtures and a 40:60 4MP/3MP solution through host-guest chemistry strategies. SCXRD analyses established the preferred guests (PYR and 4MP) to be involved in significantly shorter stabilizing classical hydrogen bonding interactions with H, explaining the selectivity behaviour of this host compound in the guest mixtures. Additionally, Hirshfeld surface considerations also explained this behaviour, but only for PYR. Additionally, thermal analyses were used to ascertain the relative thermal stabilities of the four complexes and, satisfyingly, the PYR- and 4MP-containing complexes possessed the greater thermal stabilities compared with H·2(2MP) and H·2(3MP), as was demonstrated by a comparison of their guest release onset temperatures.
Large Language Model Based Mutations in Genetic Improvement
Authors: Brownlee Alexander Edward Ian , Callan James , Even-Mendoza Karine , Geiger Alina , Hanna Carol , Petke Justyna , Sarro Federica , Sobania Dominik
Published: May 2024

Ever since the first large language models (LLMs) have become available, both academics and practitioners have used them to aid software engineering tasks. However, little research as yet has been done in combining search-based software engineering (SBSE) and LLMs. In this paper, we evaluate the use of LLMs as mutation operators for genetic improvement (GI), an SBSE approach, to improve the GI search process. In a preliminary work, we explored the feasibility of combining the Gin Java GI toolkit with OpenAI LLMs in order to generate an edit for the JCodec tool. Here we extend this investigation involving three LLMs and three types of prompt, and five real-world software projects. We sample the edits at random, as well as using local search. Our results show that, compared with conventional statement GI edits, LLMs produce fewer unique edits, but these compile and pass tests more often, with the OpenAI model finding test-passing edits 77% of the time. The OpenAI and Mistral LLMs were roughly equal in finding the best run-time improvements. Simpler prompts were more successful than those providing more context and examples. Qualitative analysis revealed a wide variety of areas where LLMs typically failed to produce valid edits: commonly including inconsistent formatting, generating non-Java syntax, or refusing to provide a solution.
Distribution-Aware Prompt Generator for Long-Tailed Vision Recognition
Authors: Liao Walter , Fang Pengfei , Ge Zongyuan , Harandi Mehrtash
Published: May 2024

We present a prompt learning framework designed to enhance the performance in computer vision task considering a particular use case where the training image dataset is confronted with highly imbalanced categorical distributions. By formulating the prompt learning as a variational problem, our model is capable of generating multiple prompts to describe a semantic (i.e, class). The motivation behind generating multiple prompts originates from the heuristic that the voting ensemble establishes a more robust aggregated learning algorithm which potentially benefits learning the tail classes where the number of the training sample is scarce. Unlike previous prompt learning techniques, which are often restricted by using a fixed set of prompts during the training and the test phase, we propose to learn the prompt distribution from which an arbitrary number of prompts can be sampled whenever required, and we named our method as “Prompt Distribution Learning (PDL)”. We will discuss and contrast various ways to formulate the variation model and thoroughly compare their performances against state-of-the-art solutions for long-tailed visual recognition. Our empirical study suggests that the proposed prompt-learning framework is beneficial for transferring a pre-trained vision-language model to long-tailed downstream visual recognition tasks while being sufficiently flexible in accommodating different designs of prompt-generating functions. Our code is publicly available at https: //github.com/Walter-pixel/Prompt-Distribution-of-CLIP-Long-Tailed-Data.