bluuebunny/crossref_metadata_2025 huggingface dataset:
The Composition of Vesicles of Non-Toxigenic Vibrio cholerae Strains, O1 El Tor and O139 Serogroups
Authors: Duvanova O. V. , Shipko E. S. , Pisanov R. V. , Tsyrulina O. A. , Chemisova O. S. , Evdokimova V. V. , Vodop’yanov A. S. , Kruglikov V. D. , Ivanova I. A. , Omel’chenko N. D. , Filipenko A. V. , Noskov A. K.
Published: December 2024

The aim of the work was to study the composition of vesicle preparations (OMV) in Vibrio cholerae strains O1 El Tor (ctxAB– tcpA– ; ctxAB– tcpA+ ) and O139 (ctxAB– tcpA– ) isolated from various sources. Materials and methods. V. cholerae strains O1 and O139 serogroups were used in the work, from which OMV preparations were obtained. The structure of OMV preparations was studied by transmission electron microscopy (TEM). Genome-wide DNA sequencing was performed on the MiSeq platform. The nucleotide and corresponding amino acid sequences of the genes were studied using bioinformatics analysis. Protein profiling was conducted using MALDI-TOF mass spectrometry. Enzymatic activities were detected using appropriate media and substrates. Determination of (surface determinants) lipopolysaccharide (LPS) and outer membrane proteins in the composition of OMV was carried out by enzyme immunoassay (ELISA). The analysis of the spectrum of fatty acids was performed by gas-liquid chromatography mass spectrometry. Results and discussion. OMV preparations have been obtained from non-toxigenic strains of cholera vibrios. TEM has revealed that OMVs are represented by spherical structures of about 40–200 nm. Genome-wide sequencing has shown that fragments of chromosomes containing genes of V. cholerae strains, O1 and O139 serogroups, from which they were isolated are present in the OMV. The bioinformatic analysis revealed differences in the structure of the ompT gene in the initial strains and in OMV obtained from V. cholerae strains O1 and O139 serogroups. The ΔompT gene of the OMV preparation from V. cholerae O139 serogroup was trunked and formed a peptide of 17 amino acid residues (-LENHHQKNREPDKEFPY-). Analysis of the OMV composition has revealed the presence of enzymes (N-acetyl-β-D-glucosaminidase and DNAazes), proteins of outer membranes (ompT and OmpU), LPS, saturated, сis/trans isomers of unsaturated fatty acids and branched fatty acids. Differences in the composition of OMV obtained from non-toxigenic strains of V. cholerae O1 and O139 serogroups have been identified.
Population Immunity to Influenza and the Risk of Emergence of a Pandemic Virus
Authors: Ilyicheva T. N. , Ivanova K. I. , Boldyrev N. D. , Danilenko A. V. , Moiseeva A. A. , Kolosova N. P. , Marchenko V. Yu. , Ryzhikov A. B.
Published: December 2024

Population immunity is a determining factor in relation to the spread of various variants of the influenza virus, and therefore is of great importance for predicting epidemics, characterizing the epidemic process and assessing the effectiveness of vaccination campaigns. The aim of the work was to monitor markers of seasonal influenza viruses and avian influenza viruses in the blood serum of residents of the Russian Federation in 2023–2024. Materials and methods. Blood serum samples from healthy donors were collected in the Siberian Federal District of the Russian Federation in October-November 2023. In addition, blood sera from people who had had contact with sick and/or dead birds and from residents of regions located on migration routes of wild waterfowl were studied in HI-test (hemagglutination inhibition) and virus neutralization. Results and discussion. It is shown that ahead of the epidemic season of 2023/2024, population immunity to influenza in the Siberian Federal District was at the level recommended by the World Health Organization (WHO) – at least 50 % of the immune population. However, among individuals who had had contact with sick and/or dead birds, humoral immunity to seasonal influenza was significantly lower – from 5 % to 30 % seropositive, depending on the region. HI-test on avian influenza viruses A/H5Nx and A/H9N2 has revealed 0 and 3.7 % of positive samples, respectively. The risk of a pandemic influenza virus emergence can be reduced by 75–100 % vaccination against seasonal influenza and monitoring antibody levels in poultry farm workers and employees of other organizations directly involved in poultry breeding and processing.
Vertebral Body Tethering in Skeletally Immature Patients
Authors: Larson A. Noelle , Todderud Julia E. , Mathew Smitha E. , Nassr Ahmad , Sebastian Arjun S. , Potter D. Dean , Milbrandt Todd A.
Published: December 2024

Background:

The purpose of this study was to report on 2-year results of vertebral body tethering (VBT), performed under a Food and Drug Administration protocol, to obtain insight into outcomes and complications.

Methods:

Forty prospectively enrolled patients with adolescent idiopathic scoliosis (AIS) who had a Sanders score of ≤4 or a Risser score of ≤2 underwent VBT for curves between 40° and 70°. Surgical, radiographic, and patient-reported outcomes were reviewed at a minimum 2-year follow-up.

Results:

Mean age at surgery was 13 (range, 10 to 16) years. The 40 patients were 90% female; 95% White, 2.5% other, and 2.5% unreported; and 92.5% non-Hispanic, 5% Hispanic, and 2.5% unreported. A mean of 8 (range, 5 to 12) levels were instrumented. Most patients were at Sanders 4 (65%) and Risser 0 (63%). Mean length of stay was 3 ± 1 days, estimated blood loss was 236 ± 158 (range, 25 to 740) mL, and operative time was 4.4 ± 1.4 hours. Mean correction of the major curve was 44% (range, 22% to 95%) on the 3-month standing radiograph, 49% at 1 year, and 46% (range, −10% to 93%) at 2 years. The mean major Cobb angle improved from 51° ± 8° (range, 40° to 70°) preoperatively to 27° ± 11° (range, 3° to 56°) at 2 years. Success at 2 years, defined by a Cobb angle of <35° and no reoperation, was seen in 30 patients (75%) and was associated with a mean Cobb angle of <35° on the first postoperative standing radiograph (p < 0.001). Twelve patients (30%) demonstrated improvement in the curve with growth. By 2 years, 2 (5%) of the patients underwent repeat surgery (1 release for overcorrection, 1 lumbar VBT for lumbar curve progression after thoracic VBT). The Scoliosis Research Society (SRS) satisfaction score improved 2 years following surgery (p < 0.001), but other SRS domains only remained stable over time. Beyond 2 years, 1 additional lumbar tether was required after thoracic VBT, 1 implant was removed, and 3 fusions were performed, for a 10% fusion rate and overall 20% reoperation rate at a mean of 3.8 ± 1.1 years of follow-up. The rate of cord breakage in the study population was 20%.

Conclusions:

In skeletally immature patients treated in the U.S. under a prospective Investigational Device Exemption, there was a 75% rate of successful outcomes at 2 years. Most correction was obtained at the time of surgery, and inadequate intraoperative curve correction was associated with a higher Cobb angle on the first postoperative standing radiograph and failure by 2 years.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Coronal Plane Alignment of the Knee (CPAK) Type Shifts Toward Constitutional Varus with Increasing Kellgren and Lawrence Grade
Authors: Kim Sung Eun , MacDessi Samuel , Song Daeseok , Kim Joong Il , Choi Byung Sun , Han Hyuk-Soo , Ro Du Hyun
Published: December 2024

Background:

Studies investigating constitutional alignment across various grades of osteoarthritis (OA) are limited. This study explored the distribution of Coronal Plane Alignment of the Knee (CPAK) types and associated radiographic parameters with increasing OA severity.

Methods:

In this retrospective cross-sectional study, 17,365 knees were analyzed using deep learning software for radiographic measurements. Knees were categorized on the basis of the Kellgren and Lawrence (KL) grade and CPAK type. Radiographic measurements were the hip-knee-ankle angle (HKAA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), arithmetic HKAA (aHKA), joint line obliquity (JLO), and joint line convergence angle (JLCA). Age-stratified analysis was performed to differentiate the impact of age on OA severity.

Results:

A shift in the most common CPAK type from II to I was found with increasing KL grade (p < 0.05). Furthermore, there was a corresponding increase in LDFA and JLCA with increasing KL grade, while HKAA, MPTA, and aHKA decreased after KL grade 2. Age exhibited limited association with LDFA and MPTA, suggesting that OA severity is the dominant factor related to the CPAK distribution.

Conclusions:

The study found a shift in CPAK type with worsening OA. It is possible that constitutional varus types are more susceptible to OA, or that their increased OA prevalence is related to anatomical changes. This analysis offers new insights into alterations in CPAK type that occur with OA and underscores the importance of understanding pre-arthritic anatomy when performing joint reconstruction.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Determining If Post-Injury Financial Distress Was Preexisting or Injury-Induced
Authors: O’Hara Nathan N. , Gage Mark J. , Loudermilk Casey , Bell Alice , Okhuereigbe David , Li Vivian , Lawrence Joshua E. , Turner Kristin E. , Kovvur Murali , O’Toole Robert V. , Slobogean Gerard P. , Mundy Lily R.
Published: December 2024

Background:

Previous research has estimated that over one-half of patients with orthopaedic trauma experience financial distress after the injury. However, it is unknown what proportion of patients lived under financial distress before the injury and, therefore, the causal effect of the injury on financial distress. This study examined changes in financial distress after the injury and factors associated with new post-injury financial distress.

Methods:

A prospective cohort study was performed at a single academic trauma center, leveraging patients’ 2-week recall of their pre-injury financial circumstances to permit a quasi-experiment design. Adult patients with a surgically treated lower-extremity fracture were included. The primary outcome was self-reported financial distress. Pre-injury financial distress was compared with financial distress in the 6 months after the injury. Multinomial logistic regression was used to identify factors associated with new financial distress after the injury.

Results:

A total of 200 study participants were enrolled (median age, 42 years [interquartile range, 32 to 59 years]); 56% of patients were male. Financial distress was present in 40% of the study participants before the injury. The fracture was associated with an absolute increase of 19% (95% confidence interval [CI], 5% to 34%; p < 0.001) in the prevalence of financial distress. New post-injury financial distress was associated with working before the injury (odds ratio [OR], 6.9 [95% CI, 2.2 to 22]; p < 0.001) and earning <$70,000 per year (OR, 3.6 [95% CI, 1.2 to 10]; p = 0.02).

Conclusions:

The findings suggest that 2 of 5 patients with a lower-extremity fracture had experienced financial distress before the injury. The prevalence of financial distress increased to 3 of 5 after the injury. Working and earning <$70,000 per year before the injury substantially elevated the patients’ risk of new financial distress post-injury. Future efforts should target interventions to reduce financial distress in this at-risk population.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Cephalomedullary Nailing for Subtrochanteric and Reverse-Oblique Femoral Fractures
Authors: Ablett Andrew D. , McCann Conor , Feng Tony , Macaskill Victoria , Oliver William M. , Keating John F.
Published: December 2024

Background:

Subtrochanteric proximal femoral fractures are generally treated with cephalomedullary nail fixation. We aimed to compare outcomes of subtrochanteric fracture fixation using a single lag screw (Gamma3 nail, GN) or dual lag screw (INTERTAN nail, IN) device.

Methods:

The primary outcome measure was mechanical failure, defined as lag screw cut-out or back-out, nail breakage, or peri-implant fracture. Secondary outcomes included reoperation for mechanical failure, deep infection, or nonunion, and technical predictors of mechanical failure. Adult patients (≥18 years of age) with a subtrochanteric proximal femoral fracture treated at a single center were retrospectively identified using electronic records. All patients who underwent fixation using either a long GN (November 2010 to January 2017) or IN (March 2017 to April 2022) were included. Medical records and radiographs were reviewed to identify operative complications.

Results:

A total of 587 patients were included: 336 in the GN group (median age, 82 years; 73% female) and 251 in the IN group (median age, 82 years; 71% female). The risk of mechanical failure was 3-fold higher in the GN group (adjusted hazard ratio [aHR], 2.87; p = 0.010), with screw cut-out (p = 0.04) and back-out (p = 0.04) only observed in the GN group. We observed a greater risk of reoperation for mechanical failure in the GN group, but this did not achieve significance (aHR, 2.02; p = 0.16). Independent predictors of mechanical failure included varus malalignment of >5° for cut-out (aHR, 17.43; p = 0.012), a tip-to-apex distance of >25 mm for back-out (aHR, 9.47; p = 0.019), and shortening of >1 cm for peri-implant fracture (aHR, 5.44; p = 0.001).

Conclusions:

For older patients with subtrochanteric and reverse-oblique femoral fractures, the dual lag screw design of the IN nail was associated with a lower risk of mechanical failure compared with the single lag screw design of the GN nail.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Glucagon-Like Peptide-1 Receptor Agonists Decrease Medical and Surgical Complications in Morbidly Obese Patients Undergoing Primary TKA
Authors: Kim Billy I. , LaValva Scott M. , Parks Michael L. , Sculco Peter K. , Della Valle Alejandro G. , Lee Gwo-Chin
Published: December 2024

Background:

Weight optimization methods in morbidly obese patients with a body mass index (BMI) of ≥40 kg/m2 undergoing total knee arthroplasty (TKA) have shown mixed results. The purpose of this study was to evaluate the effect of perioperative use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with a BMI of ≥40 kg/m2 undergoing primary TKA.

Methods:

Using an administrative claims database, patients with morbid obesity undergoing primary TKA were stratified into GLP-1 RA use for 3 months before and after the surgical procedure (treatment group) and GLP-1 RA non-use (control group), and were matched on the basis of patient age, gender, diagnosis of type-2 diabetes mellitus, and Charlson Comorbidity Index (CCI). In addition, these groups were compared with a contemporaneous cohort of patients undergoing TKA with a BMI of 35.0 to 39.9 kg/m2. Outcomes including infection, complications, revision, and readmission were compared between the matched cohorts.

Results:

There were significant decreases in the rates of 90-day periprosthetic joint infection (PJI) (1.0% compared with 1.8%; p = 0.037), any medical complications (10.6% compared with 12.7%; p = 0.033), pulmonary embolism (<0.4% compared with 0.6%; p = 0.050), and readmissions (5.3% compared with 8.9%; p < 0.001) in patients with a BMI of ≥40 kg/m2 who were taking GLP-1 RA versus the control group who were not. There were no differences in the 2-year rates of surgical complications (p > 0.05) between these groups. Compared with obese patients (BMI of 35.0 to 39.9 kg/m2), patients who had a BMI of ≥40 kg/m2 and were taking a GLP-1 RA did not have increased rates of infection or 90-day or 2-year complications (p > 0.05).

Conclusions:

GLP-1 RA administration for at least 90 days prior to and after primary TKA in patients with a BMI of ≥40 kg/m2 was associated with reductions in the risks of 90-day PJI, any medical complications, and readmission. Additionally, the reduced complication rate that was achieved was similar to that of obese patients with a BMI of 35.0 to 39.9 kg/m2 undergoing TKA. Randomized clinical trials are needed to define the true effect of these agents on clinical outcomes following TKA.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Principle of Education According to The Perspective of Hasan bin Ali Al-Hajjajy And John Dewey
Authors: Billah Akbar Aisya , Ulum M. Miftahul
Published: December 2024

Education is a basic need and right of every human being. With this education, humans get a decent and good life. The educational building stands strong and firm on a solid foundation of thought. This is where educational thinkers' urgency is in supporting these buildings' establishment. Not only related to the building's strength, style, and model is also very dependent on the style of thought of the characters. This research is a literature study or library research. Data were taken from related literature in books, journals, and various sources. The data is then processed and analyzed critically and in-depth using content analysis. The study results show that there are different perspectives on the principles of education according to Islam, represented by Hasan bin Ali Al-Hajjajy, and a Western perspective, represented by John Dewey. Each perspective gave birth to different styles and education models, so the products produced also differ.
The Influence of Mental Health, Study Habits and Achievement Motivation on Students’ Success at MTsN 4 Surabaya
Authors: Ida Fitriyah Eting , Darmawan Didit
Published: December 2024

This study aims to investigate the effect of mental health and study habits on student achievement at State Tsanawiyah Madrasah 4 Surabaya City. The study population included all State Tsanawiyah Madrasah 4 Surabaya City students, totalling 704 students. The research sample was randomly drawn from students in Class VII, totalling 277 students. Data analysis was conducted using the statistical method of regression analysis to identify the extent of the influence of the three independent variables on the dependent variable. The results showed that students' mental health has a significant influence on learning achievement. Students with good mental health tend to be able to cope with pressure and stress, allowing them to focus and concentrate better during the learning process. Students' study habits were also shown to play an important role in shaping learning achievement. Regular and structured study habits help students to effectively manage time and study tasks, creating the basis for optimal achievement. In conclusion, mental health and study habits play a crucial role in shaping student achievement.
Idāratu Tanfīżi Barnāmaji Ta’līmi al-Lughah al-`Arabiyyah fi Markazi al-Lughah al-`Arabiyyah bi Puncak Darussalam Madura
Authors: Fithtriyah Aidah , Rosyada Amrina , Hadziq Muhammad Fadhil , Mubarok Khusnul , Hilmi Danial , Rasuliy Mohammad Walid
Published: December 2024

This study aims to determine the management of the implementation of the Arabic language learning program at Markaz Lughah Arabiyah Puncak Darussalam Madura and also to find out the problems faced in the implementation of the program. This research uses descriptive qualitative method. Data collection through observation techniques, semi-structured interviews and documentation. While analyzing the data through the analysis theory of Miles, Huberman, and Saldana which consists of data condensation, data presentation and conclusion drawing. The results showed that the management of the implementation of the Arabic language learning program at Markaz Lughah Arabiyah Puncak Darussalam Madura went well, seen from the activities of the students were very enthusiastic in participating in the program, namely the students could follow the activities until the specified time limit. In order to maximize language learning, Arabic is used as a daily communication tool. The problems faced by the markaz are the lack of teaching staff, limited facilities and learning resources, and limited learning time which affects the effectiveness of the learning process. Despite the shortcomings, the learning program held by the markaz can still run smoothly and well, where within the specified time (two semesters / one year), the students have been able to master Arabic well.
Namāżiju at-Ta’līm `Ala Asāsi Manhaj Merdeka fi Qismi Ta’līm al-Lughah al-Arabiyyah bi Jāmi’ati Prof. K.H Saifudin Zuhri Purwokerto
Authors: Ruswatie Ade , Mukroji Mukroji , Hafidz Rif’an Ali , Fiqiyah Maskanatul
Published: December 2024

The educational process in the Arabic Language Education Department at the State Islamic University of Professor Kiai Haji Saifuddin Zuhri, Purwokerto, was conducted based on the Merdeka curriculum. This curriculum includes various models, such as the problem-based model, the project-based model, and the student-interest-based model. The educational process in the Arabic Language Education Department was carried out using the Merdeka curriculum, with several models depending on the teacher's capabilities. This research aimed to reveal the models used in the educational process based on the Merdeka curriculum. The researchers employed a qualitative approach in this study, which was a field study. They chose interviews, observations, and documentation to collect data. The data analysis method used was data reduction, presentation, and then drawing conclusions. After conducting the study, the researchers found that the models used in the educational process in the Arabic Language Education Department at the State Islamic University of Professor Kiai Haji Saifuddin Zuhri, Purwokerto, were project-based learning in some lessons, project-based learning in others, inquiry-based learning, discovery-based learning, and collaborative learning, which were applied frequently across all subjects in the Arabic Language Education Department.
Fa’āliyyatu Istkhdāmi Wasā`il “UNO Sharf” fī Ta’līmi Darsi as-Ṣarf li as-Ṣaf as-Tsāni bi Kulliyyati al-Mu’allimīn al-Islāmiyyah bi Ma’hadi ar-Ridho Sentul
Authors: Fata Khoirul , Tsani Fadhilah Akbar Adyana , Ramadhansyah Muhammad Faisal
Published: December 2024

Learning media "UNO Sharf" is a learning media of small cards modified from the UNO card game as a tool used by teachers in teaching or assisting teachers in providing understanding of certain concepts in learning, especially in Shorf lessons. In the initial observation at the institution, especially during teaching and learning activities, it was still faced with various problems, which affected the students' low scores. With this problem, researchers tried to provide a solution in the form of learning media "UNO Sharf" in Sharf lesson. The research was conducted using quantitative pre-experimental methods by design and the collection of data through test. From this study, it was concluded that the results were obtained, namely variable (X) learning media "UNO Sharf" effective if applied to variable (Y) class 2 KMI Sharf Lesson at the Kulliyyatul Mu’allimin al Islamiyyah Ar-Ridho Sentul. This can be seen from the results of the analysis test using the Wilcoxon Signed Rank Test method which is intended with a significance of 0.000 < 0.050, meaning that Ho is rejected and Ha is accepted. Then the average positive rank of 25 students was 13.00. Based on valid test results, researchers suggest that the learning media "UNO Sharf" can be used as a learning medium at the Kulliyyatul Mu’allimin al Islamiyyah Ar-Ridho Sentul create a good teaching and learning atmosphere and make teachers more creative and innovative.
‘Where soft skills are (not) developing…’: A study of graduates’ skills and the role of university in preparing students for the labour market in Hungary
Authors: Kocsis Zsófia , Pusztai Gabriella
Published: December 2024

In the 21st century, the need to develop skills has gained significance. Most education systems equip graduates with the cognitive skills needed to enter the labour market. However, it is soft skills that enable young graduates to become potential employees. Hungarian higher education is characterised by a teacher-centred approach, which is less conducive to the development of soft skills. Our research investigates graduates’ skills and the extent to which their skills are in alignment with the requirements of the workplace. The Fresh Graduate Survey 2020 database was used, while our interview survey provides nuances to the results of the secondary analysis. We also analyse how one Hungarian higher education institution has supported students’ transition to the labour market. Data show that the competences considered important in the labour market are not always the same as the skills that graduates most often possess. There is a considerable gap between expected and existing skills in the following areas: problem-solving, time management, practical expertise and conflict management. These skills are particularly important in the labour market, but graduates are less likely to have them. The results of the quantitative research are also nuanced by the interviews, which show that higher education provides a good foundation but does not sufficiently focus on the development of soft skills. The results of the qualitative research highlight a number of shortcomings in key areas, the development of which is important not only at the level of individuals but also in the long term in view of the prestige of university education.
The global carbon balance of forests based on flux towers and forest age data
Authors: Ciais Philippe , Yao Yitong , Besnard Simon , Yue Chao , Poulter Benjamin , Jung Martin , Chave Jerome , Stoy Paul C. , Reichstein Markus , Herold Martin , Piao Shilong , Carvalhais Nuno
Published: December 2024

Flux towers worldwide record significant carbon sinks in forests. Still, most sites are situated over young or middle-aged stands at, or close to, the peak of carbon uptake along their successional cycle. As a result, upscaling forest Net Ecosystem Productivity (NEP) — the difference between gross primary production (GPP) and ecosystem respiration (ER) — from existing sites to the global scale has been challenging, in contrast to the successful upscaling of GPP and the associated surface energy fluxes. In this study, we combine a recently released forest age map 1, empirical NEP-age relationships and environmental predictors, and machine-learning algorithms to generate gridded estimates of forest NEP for the period circa 2010. The quantified global forest NEP is 6.4 ± 2.0 PgC year-1. After subtracting carbon losses not measured by flux towers, including fire emissions, harvested biomass, fluvial leaching, and non-CO2 gases released to the atmosphere, we obtain a global net carbon balance of forests remaining forests (NBP) close to 3.0 ± 2.0 PgC year-1. This value is consistent with those based on forest inventories 2 and atmospheric inversions 3. We report a carbon sink of 1.5 ± 0.5 PgC year-1 for temperate forests, a value twice as large as that inferred from inventories, largely because inventories may underestimate soil carbon accumulation. Boreal forests show a small source of -0.1 ± 0.3 PgC year-1. In contrast, tropical forests not subject to degradation and deforestation have an NBP sink of +1.6 ± 1.1 PgC year-1, larger than what is inferred from biomass inventories. Half of the tropical forest sinks are located in dry forests and woodlands, which have smaller productivity than humid forests but accumulate carbon from a younger age due to frequent fire disturbances. Our results bring a new constraint on the global carbon budget, highlighting the importance of accounting for forest age in upscaling local flux tower data.
Biomimic opto-nanobiointerface enables multiscale biomodulation
Authors: Chen Menglin , Müller Christoph , Zhang Yuge , Meng Lingyuan , Kalatanova Anna , Madsen Jesper Guldsmed , Klompmaker Kjeld Kaj , Jakobsen Thomas Stax , Joergensen Asbjoern Cortnum , Askou Anne Louise , Huang Ge , Li Wen , Davidsen Rasmus Schmidt , Bek Toke , Hatzakis Nikos , Corydon Thomas , Leinonen Henri O , Tian Bozhi , Dong Mingdong
Published: December 2024

Virtually all organic material on Earth has been produced converting solar energy through photosynthesis in chloroplasts, a sack-like, double membrane organelle in plants and algae, where transmembrane electron transfer occurs from lumen to stroma. Although animals hardly harness the power of photosynthesis, their bioelectrical signals extensively regulate complex electrophysiological behaviors, rendering it a superior target for biomedical innovation. Here a crude structural mimicry of chloroplast has led us to discover that hollow sphere graphitic carbon nitride nanoparticles (hg-C3N4 NPs) endowed non-genetic, subcellular and intercellular photo-modulation of various excitable and non-excitable cells, accumulatively achieving modulation at tissue/organ function level. The homogeneous hg-C3N4 NPs showed photo-responsiveness via photoelectrochemical and photothermal mechanisms under photocurrent measurement. The hg-C3N4 NPs can be spontaneously internalized with excellent cytocompatibility. Using a focusing laser, the hg-C3N4 NPs enable intracellular optical stimulation with subcellular resolution, inducing calcium transient release in multiple cells and propagation in primary cardiomyocytes and cardiac fibroblasts. At multicellular scale, optical pacing and synchronization of cardiomyocyte beating is achieved facilely by LED. Further, we demonstrate that hg-C3N4 NPs can be safely injected into mouse eyes, restoring light sensitivity in blind mice. Finally, application of hg-C3N4 NPs to porcine retinal tissue ex vivo confirmed their modulation capability to reactivate RGCs activity under LED photostimulation. Taken together, these nanostructured biomimic semiconductor NPs offer high resolution, leadless optical probing, non-invasive delivery and great biocompatibility, serving as a versatile tool for addressing a range of complex biomedical challenges through subcellular, intercellular and tissue-level photo-modulation across a broad spectrum of scales.
Evaluation of Drug Lag and Drug Loss in Japan: Participation in Global Phase III Oncology Trials
Authors: Shiga Kaname , Shibata Taro , Miyata Toshio
Published: December 2024

Background: Despite efforts to mitigate drug lag, discrepancies in drug approval timelines persist between Japan and the US, and increase in unapproved drugs has become a significant challenge. This study aimed to evaluate potential drug lag and drug loss by assessing Japan's participation in global phase III multinational/multiregional clinical trials (MRCTs) targeted cancers.
Methods: Phase III MRCTs of anticancer drugs initiated between 2008 and 2022 were collected. Information of participant countries, study sponsor, study design, and cancer type were collected and analyzed by. logistic regression analysis to identify factors affected Japan’s participation.
Results: Of 999 phase III MRCTs, Japan's participation every 5 year increased over 15 years (2008-2012: 34.3%, 2013-2017: 51.6%, 2018-2022: 60.2%), while Japan’s non-participation numbers didn’t change (2008-2012: 157, 2013-2017: 167, 2018-2022: 165). In the multivariate logistic regression analysis, the absence of an operational base in Japan and minor cancers were negatively associated with Japan’s participation in phase III MRCTs. Japan’s participation was also associated with some cancer organs and drug modalities.
Conclusion: Potential future drug lag and increases of unapproved drug were expected to increase. Since inclusion of Japan in MRCTs results in shorter or no approval lag, Japan should promote to make the circumstances where small overseas companies can include Japan in MRCTs.
Hearing outcomes in canal wall up versus canal wall down mastoidectomy
Authors: Bhardwaj Yavan , Bhardwaj Heemani , Amin Saddaf , Mahmood Tariq
Published: December 2024

Introduction:
Chronic suppurative otitis media (CSOM) is a common problem seen in numerous patients with high rate of morbidity and psychosocial impact. The mainstay of management remains surgical. The two surgical techniques used globally for management of patients with middle ear cleft pathology are canal wall up and canal wall down mastoid surgeries. Deciding factors for type of procedure done depend on; the interest of operating surgeon, patient’s general health and age, extent and type of pathology in the middle ear and also considering functional hearing outcomes of both the surgical procedures.
Objective
The aim of the present study was to compare the hearing outcomes and graft take up rate between canal wall up and canal wall down mastoidectomy procedures.
Methods
The present prospective study was conducted in the Department of Otorhinolaryngology and Head Neck Surgery, a tertiary care multi-speciality teaching hospital from October 2018- August 2020. The study group included 100 patients. In this study, all the patients underwent mastoidectomy with tympanoplasty using temporalis fascia graft. Intact canal wall mastoidectomy was done in patients with localized cholesteatoma while canal wall down mastoidectomy was done in patients having extensive disease. Regular follow up was done every week for first 3 weeks, later at 6th week, 3rd month, 6th month and 1 year. Study Design: Comparative study.
Results
A total of 100 patients were included in the study. The age of the patients 10 to 50 years with a mean age of 18.7 ± 15 years with male to female ratio 7:10. In the present study, graft take up in canal wall up mastoidectomy was 66.6% as compared to 33.4% in canal wall down procedure which was significantly higher (ꭓ2=10.72, p = 0.0011). Hearing gain in canal wall up procedure (17.02 ± 8.51db) was higher as compared to canal wall down mastoidectomy (10.3 ± 6.98), (t = 4.22, p < 0.001). It was statistically significant. Recurrence was seen in 1 patient who had undergone canal wall up surgery.
Conclusions
Canal wall down surgery is a safer option in the matter of residual disease and recurrence. Canal wall up surgery though may need a second look procedure, but there are better results of graft take up rate and the post-operative hearing as compared to canal wall down surgery
Remote group intervention for adults with cancer-related cognitive impairment: A feasibility study.
Authors: Hamami Chenanit , Peretz Tamar , Nahum Mor , Maeir Talia , Maimon Ofra , Gilboa Yafit
Published: December 2024

Purpose This study aimed to examine the feasibility of a remote group intervention, Computerized Retraining and Functional Treatment Group (CRAFT-G), among adults with cancer-related cognitive impairment (CRCI). CRAFT-G is designed to improve occupational performance, objective and subjective cognitive functions, quality of life (QoL), and sense of loneliness.Method A single-arm quasi-experimental design using mixed quantitative and qualitative methods was applied. Five cancer survivors with CRCI, aged 30 to 57 years, received the CRAFT-G intervention, which includes 6 weekly group sessions along with 18 sessions of individualized computerized cognitive training (CCT; 3 per week). Feasibility was measured in terms of recruitment, retention, adherence, acceptability, and potential effectiveness. Outcome measures were administered at baseline and post intervention.Results The recruitment rate was 35% (6/17), and the retention rate was 83.2%. Partial adherence was found to the group sessions (80%) and to the CCT (40%). Participants expressed moderate to very high satisfaction with the intervention. Three main themes emerged from the feedback interviews: (a) group dynamic and therapeutic context, (b) intervention components, and (c) client factors. Significant improvements in occupational performance and clinically significant improvements in self-perceived cognitive function were also found, demonstrating potential effectiveness.Conclusion The results support the feasibility and potential effectiveness of the CRAFT-G among adults with CRCI. A controlled, larger trial should be conducted to validate these results.Implications for Cancer Survivors: A combined intervention approach of an occupation-based intervention along with cognitive training and psychoeducation about CRCI applied in remote group format should be considered when treating adults with CRCI.
A Diagnostic model based on MRI for Meniere's disease: a multicenter study
Authors: Chen Xinyi , Zhao Yanfeng , Han Yunchong , Wei Kai , Cheng Shufang , Ye Yongjun , Feng Jie , Huang Xinchen , Xu Jingjing
Published: December 2024

Purpose
To explore the diagnostic performance of delayed post gadolinium enhancement MRI (DEMRI) in the diagnosis of Meniere's disease (MD), and to establish an effective MRI diagnostic model.
Materials and methods
This retrospective multicenter study evaluated DEMRI descriptors of patients with Ménièriform symptoms examined consecutively from May 2022 to May 2024. A total of 162 ears (95 MD ears, 67 control ears) were enrolled in this study. Each ear was randomly allocated to a training set (n = 98) and a validation set (n = 64). Logistic regression determined three models for the diagnosis of MD in the training cohort. AUC was applied to evaluate the diagnostic performance of different models. Delong test was used to compare the AUC estimates between the different diagnostic models.
Results
The proposed DEMRI diagnostic model demonstrated good diagnostic performance in both the training (AUC, 0.907) and the validation cohort (AUC, 0.887), outperforming the clinical diagnostic model (Z = 2.503, p = 0.01231; 95%CI:0.033–0.269) in the validation cohort. The AUC value of DEMRI model was higher than combined DEMRI-clinical model in the validation cohort (AUC, 0.796) as well, but there was no statistically significant difference (Z = -1.9291, p = 0.05372). In the training set, the sensitivity, specificity, and accuracy of the DEMRI model were 78.9%, 88.5% and 82.8%, respectively.
Conclusion
A diagnosis model based on DEMRI features for MD diagnosis efficiency was higher than that of clinical variables alone. Therefore, DEMRI should be recommended when MD is suspected because of its significant potential in the diagnosis of MD.
Statistical estimation of carbon dioxide emissions from merchant ships on Sub-Saharan African routes
Authors: Kwame Eyram , Viban Berinyuy Litika , Akyere Grace Nuako
Published: December 2024

Sub-Saharan Africa is the region of Africa located below the Sahara. The region contains forty-nine countries, sixteen are landlocked, while the rest have coastal boundaries, and seaports. Sub-Saharan African countries are classified as either developing or least developed by United Nation Trade and Development (UNCTAD). The global trade participation of these countries is facilitated by merchant shipping. With increasing awareness of the exponential growth of the concentration of greenhouse gases (GHGs) in the atmosphere, there is a pressing need to mitigate the effects of climate change by proactively quantifying and minimizing emissions from ships to achieve the 2050 net-zero GHGs emission target of IMO. This paper uses parameter estimation technique, to statistically estimate carbon dioxide emissions from merchant ships on sub-Saharan African routes to be at least 185.87 million tonnes, which is equivalent to 17.27% of the world's annual shipping CO2 emissions. The paper concludes that these routes contribute significantly to CO2 emissions leading to global warming. Therefore, port authorities should extensively regulate vessels visiting their ports by enforcing stringent emission standards and imposing penalties for non-compliance.
Forest canopy structure response to climate change from a global perspective
Authors: Mao Xuegang , Liu Hongpeng , Wang Chengyuan Wang , Zhang Zhiyang , Liu YuanLiu , Liu Chengyin , Cao Rong , Wang Enheng Wang
Published: December 2024

The structure of the forest canopy plays a pivotal role in determining the response of forest ecosystems to climate change. However, the large-scale impact of climate change on canopy structure remains inadequately understood, particularly at the global level. This knowledge gap can be attributed mainly to the lack of reliable methods for consistently monitoring changes in canopy structure over extended periods. To address this challenge, we developed a global Forest Canopy Structure Index (FCSI) by synthesizing four remotely sensed vegetation indices, thus enabling the mapping of spatial and temporal dynamics of canopy structures across the globe. Furthermore, we investigated how the canopy structures of six distinct forest types respond to ten key climate variables. Our results reveal substantial latitudinal variation in FCSI: in the Northern Hemisphere, FCSI decreases by approximately 0.002 for every 1° increase in latitude, while in the Southern Hemisphere, the decline is more pronounced, approaching 0.004. The only forest types exhibiting an overall increase in FCSI from 2005 to 2021 are Deciduous Broadleaf Forests, Deciduous Needleleaf Forests, and Woody Savannas, yet only 27.91% of global forests show a significant rise in FCSI. Precipitation emerged as the most influential factor driving changes in FCSI, while diurnal temperature range exerted a robust positive effect on canopy structure across all six forest types. This study introduces novel methodologies for large-scale quantification of forest canopy structure and provides valuable insights into how forest ecosystems respond to and adapt to climate change.
Shared Genetic Architecture Between COVID-19 Severity and Alzheimer's Disease Across European and African Ancestries
Authors: Chen Jingchun , Cammann Davis , Liu Tingwei , Liu Yimei , Cummings Melika , Chen Xiangning , Oh Edwin , Rotter Jerome
Published: December 2024

The global outbreak of COVID-19, caused by the SARS-CoV-2 virus, has been linked to long-term neurological complications, including an increased risk of Alzheimer's disease (AD) among older adults. However, the precise genetic impact of COVID-19 on long-term AD development remains unclear. This study leveraged genome-wide association study (GWAS) data and genotype data to explore the genetic association between AD and various COVID-19 phenotypes across European ancestry (EA) and African ancestry (AA) cohorts, and the possibility of a causal effect of COVID-19 on AD. We first calculated polygenic risk scores (PRSs) of three COVID-19 phenotypes in AD cases and controls from both EA and AA populations, then determined the genetic associations between COVID-19 PRSs and AD by logistic regression analyses with or without adjusting for age, sex, and APOE genotypes. Significant positive associations were found between AD diagnosis and COVID-19 PRSs in both populations, with the strongest associations identified in the AA population. However, Mendelian randomization (MR) analyses revealed no evidence of a causal effect of COVID-19 phenotypes on AD liability. We explored this finding further through the analysis of shared genomic regions between the COVID-19 phenotypes and AD and found a region of overlap on chromosome 17 that was highly pleiotropic for traits implicating immune function, psychiatric disorders, and lung function phenotypes. These findings suggest that while COVID-19 and AD share overlapping polygenic contributions involving peripheral genes across multiple traits, they lack a direct connection involving core genes that drive the development of their respective pathologies.
Electrical and mechanical dyssynchrony in pre-capillary pulmonary hypertension without complete bundle branch block: a comparison between electrocardiogram and two-dimensional echocardiography
Authors: Liu Bing-yang , Hu En-ci , Xue Lin , Wu Wei-chun , Yang Yi-cheng , Yang Bei-lan , Liang Yan-ru , Zeng Qi-xian , Yang Tao , Zhao Qing , Luo Qin , Zhao Zhi-hui , Liu Zhi-hong , Xiong Chang-ming
Published: December 2024

Background:To explore the correlation between electrical and mechanical dyssynchrony of right ventricle (RV)in pre-capillary pulmonary hypertension (PcPH) patients, and further compare their capability in predicting risk stratification.
Methods: We consecutively enrolled PcPH patients at Fuwai Hospital from April 2017 to March 2018, then classified them into low and non-low risk groups based on recommendations of 2015 European Society of Cardiology Guidelines. RV mechanical dyssynchrony were measured using off-line softwares (GE EchoPAC version 201), referred to as RV-SD6. Electrical dyssynchrony, represented as QRS duration, was measured manually from the chest lead V2 with electronic calipers.
Results: Sixty-six PcPH patients (average 35 years, 19 males and 47 females) were finally enrolled, 37 in low-risk group, while 29 in non-low-risk group. QRS duration was significantly correlated with RV-SD6 (r = 0.25, P = 0.047). Both RV-SD6 and QRS duration significantly correlated with N-terminal pro-brain natriuretic peptide (r = 0.44, P＜0.001 vs r = 0.26, P = 0.039). Furthermore, RV-SD6 (area under curve, AUC 0.75, 95% CI 0.64–0.87, P ＜0.001) and QRS duration (AUC 0.65, 95% CI 0.52–0.78, P = 0.036) both had the potential to predict non-low risk stratification. Multivariate Logistic regression analyses identified RV-SD6 (OR: 1.02, 95% CI: 1.01–1.03, P = 0.009) and QRS duration (OR: 1.07, 95% CI: 1.00–1.15, P = 0.045) as independent predictors of non-low risk of PcPH patients.
Conclusion: RV mechanical dyssynchrony presented by RV-SD6 correlates with QRS duration and has a better capability in predicting risk stratification in PcPH patients without complete bundle branch block.
The study and predictive analysis of the burden of blood stream infection diseases in China
Authors: Zhang Xiaoyu , Zhang Xifan , Tian Sufei , Guo Feng , Zhang Jingping , Chen Baiyi , Zhang Deng , Zhang Xin
Published: December 2024

Background: BSI are one of the leading causes of infection-related mortality worldwide. However, epidemiological data related to BSI in China remain very limited.
Methods: Based on the GBD database, a systematic analysis was conducted on the epidemic trends, pathogen spectrum, and the current status of AMR related to BSI in China for the year 2021. Additionally, an ARIMA time series model was constructed to predict the trend of the disease burden associated with BSI in China from 2022 to 2035.
Results: In terms of pathogens, the top five pathogens causing deaths due to BSI in China are as follows: Staphylococcus aureus, Escherichia coli , Streptococcus pneumoniae , Pseudomonas aeruginosa , and Acinetobacter baumannii . There are significant differences in the pathogens causing BSI across different age groups. The disease burden is heaviest in the elderly population aged 70 and above. Among children under five years old, Staphylococcus aureus, Streptococcus pneumoniae, and Candida species are predominant. From 1990 to 2021, there was a gradual decline in the mortality rate among BSI patients across different age groups. However, as age increases, the burden of BSI gradually increases, particularly in individuals aged 70 and above, where the disease burden is significantly higher compared to other populations.
Conclusion: From 1990 to 2035, the overall mortality rate of BSI is gradually declining. However, the future changes in BSI mortality rates will primarily be influenced by population size and changes in age structure. BSI and its associated health issues remain significant challenges that require ongoing attention.