bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of microbial-derived biosurfactants for oral applications–a systematic review
Authors: Khairunnisa Z. , Tuygunov N. , Cahyanto A. , Aznita W. H. , Purwasena I. A. , Noor N. S.M. , Azami N. H. , Zakaria M. N.
Published: June 2024

Background

Biosurfactants are amphiphilic compounds produced by various microorganisms. Current research evaluates diverse types of biosurfactants against a range of oral pathogens.

Objectives

This systematic review aims to explore the potential of microbial-derived biosurfactants for oral applications.

Methodology

A systematic literature search was performed utilizing PubMed-MEDLINE, Scopus, and Web of Science databases with designated keywords. The results were registered in the PROSPERO database and conducted following the PRISMA checklist. Criteria for eligibility, guided by the PICOS framework, were established for both inclusion and exclusion criteria. The QUIN tool was used to assess the bias risk for in vitro dentistry studies.

Results

Among the initial 357 findings, ten studies were selected for further analysis. The outcomes of this systematic review reveal that both crude and purified forms of biosurfactants exhibit antimicrobial and antibiofilm properties against various oral pathogens. Noteworthy applications of biosurfactants in oral products include mouthwash, toothpaste, and implant coating.

Conclusion

Biosurfactants have garnered considerable interest and demonstrated their potential for application in oral health. This is attributed to their surface-active properties, antiadhesive activity, biodegradability, and antimicrobial effectiveness against a variety of oral microorganisms, including bacteria and fungi.
Efficacy and safety of eliapixant in endometriosis-associated pelvic pain: the randomized, placebo-controlled phase 2b SCHUMANN study
Authors: Parke Susanne , Gude Kerstin , Roth Katrin , Messina Fabrizio
Published: June 2024

Background

The SCHUMANN study evaluated the efficacy and safety of the selective P2 × 3 antagonist eliapixant in patients with endometriosis-associated pelvic pain (EAPP).

Methods

SCHUMANN was a randomized, placebo- and active comparator-controlled, double-blind to placebo and open-label to comparator, parallel-group, multicenter, dose-finding phase 2b study. The participants were women with surgically diagnosed endometriosis who fulfilled defined EAPP criteria. Participants were randomized 1:1:1:1 to twice daily (BID) 25 mg, 75 mg, or 150 mg oral eliapixant or a placebo for 12 weeks. An exploratory once-daily elagolix 150 mg treatment group was also included. The primary endpoint was the absolute change in mean worst EAPP from baseline to the end of intervention (EOI).

Results

Overall, 215 participants were randomized for treatment (44 to eliapixant 25 mg, 44 to eliapixant 75 mg, 43 to eliapixant 150 mg, 43 to a placebo, and 41 to elagolix 150 mg). For safety reasons, the study was terminated early; both treatment and enrollment stopped immediately, producing less than 50% of the planned number of completers. The study found no significant differences in EAPP reduction from baseline between groups and no significant dose-response model. The elagolix 150 mg group showed better pain reduction than any of the other groups. No new safety signals were observed, relative to the previously known safety profile of eliapixant, which was generally well tolerated. However, one case of moderate and probably drug-induced liver injury in a participant receiving eliapixant 150 mg BID supported the association between eliapixant and a potential increase in liver function values, defined before the start of the phase 2 program.

Conclusions

This study did not meet its primary objective as no statistically significant or clinically relevant differences in changes of mean worst EAPP from baseline were observed between treatment groups. The single observed case of moderate, probably drug-induced liver injury was the second case in the eliapixant phase 2 program conducted in the following indications: refractory or unexplained chronic cough, diabetic neuropathic pain, overactive bladder, and EAPP. Due to this, the benefit-risk ratio for the study was no longer considered to be positive.

Clinical trial registration

ClinicalTrials.gov identifier NCT04614246; registered November 3, 2020.
Effects of exercise on sex steroid hormones (estrogen, progesterone, testosterone) in eumenorrheic females: A systematic to review and meta-analysis
Authors: Shahid Wajiha , Noor Rabiya , Bashir Muhammad Salman
Published: June 2024

Background

The sex steroid hormones fluctuate during the menstrual cycle, which affects the strength and postural stability of females and leads to injuries and risk of falls. These hormones may be modulated by exercise to impact the overall health of females.

Objective

To determine the effects of exercise on sex steroid hormones in eumenorrheic females.

Methods

This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines in Lahore, Pakistan. The full-length articles were searched using these databases/search engines (PubMed, Web of Science and Google Scholar, Sci-Hub). Randomized controlled trials along with single group experimental studies were also included. All types of exercises were compared with no exercise in the control group. The Cochrane Risk of Bias assessment tool assessed and screened the articles. The data were then analyzed. The primary outcomes were the levels of estrogen, progesterone and testosterone.

Results

Eleven studies were included (5 randomized controlled trials and 6 quasi-experimental studies). The effects of exercise on free estradiol concentration and serum progesterone level were not significant [p = 0.37 (SMD = 0.33, 95% CI = 0.14 to 0.74, I2 = 0%) and p = 0.84 (S.D= -0.65, C.I= -6.92 to 5.62, I2 = 94%)] respectively, whereas, the effects on testosterone levels were significant [p value < 0.00001 (M.D = 0.89, 95% C.I= -2.16 to 3.95, I2 = 94%)].

Conclusion

A blinded randomized controlled trial should be conducted in which a structured approach should be followed by women along with warm-ups, cool down and rest intervals.

Trial registration number

The systematic review was registered prospectively on PROSPERO with registration number CRD42023473767.
Delineating excess comorbidities in idiopathic pulmonary fibrosis: an observational study
Authors: Ozaltin Burcu , Chapman Robert , Arfeen Muhammad Qummer Ul , Fitzpatick Natalie , Hemingway Harry , Direk Kenan , Jacob Joseph
Published: June 2024

Background

Our study examined whether prevalent and incident comorbidities are increased in idiopathic pulmonary fibrosis (IPF) patients when compared to matched chronic obstructive pulmonary disease (COPD) patients and control subjects without IPF or COPD.

Methods

IPF and age, gender and smoking matched COPD patients, diagnosed between 01/01/1997 and 01/01/2019 were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort at the first date an ICD-10 or read code mentioned IPF/COPD. A control cohort comprised age, gender and pack-year smoking matched subjects without IPF or COPD. Prevalent (prior to IPF/COPD diagnosis) and incident (after IPF/COPD diagnosis) comorbidities were examined. Group differences were estimated using a t-test. Mortality relationships were examined using multivariable Cox proportional hazards adjusted for patient age, gender and smoking status.

Results

Across 3055 IPF patients, 38% had 3 or more prevalent comorbidities versus 32% of COPD patients and 21% of matched control subjects. Survival time reduced as the number of comorbidities in an individual increased (p < 0.0001).

In IPF, prevalent heart failure (Hazard ratio [HR] = 1.62, 95% Confidence Interval [CI]: 1.43–1.84, p < 0.001), chronic kidney disease (HR = 1.27, 95%CI: 1.10–1.47, p = 0.001), cerebrovascular disease (HR = 1.18, 95%CI: 1.02–1.35, p = 0.02), abdominal and peripheral vascular disease (HR = 1.29, 95%CI: 1.09–1.50, p = 0.003) independently associated with reduced survival. Key comorbidities showed increased incidence in IPF (versus COPD) 7–10 years prior to IPF diagnosis.

Interpretation

The mortality impact of excessive prevalent comorbidities in IPF versus COPD and smoking matched controls suggests that multiorgan mechanisms of injury need elucidation in patients that develop IPF.
Comprehensive network of stress-induced responses in Zymomonas mobilis during bioethanol production: from physiological and molecular responses to the effects of system metabolic engineering
Authors: Asefi Shaqayeq , Nouri Hoda , Pourmohammadi Golchehr , Moghimi Hamid
Published: June 2024

Nowadays, biofuels, especially bioethanol, are becoming increasingly popular as an alternative to fossil fuels. Zymomonas mobilis is a desirable species for bioethanol production due to its unique characteristics, such as low biomass production and high-rate glucose metabolism. However, several factors can interfere with the fermentation process and hinder microbial activity, including lignocellulosic hydrolysate inhibitors, high temperatures, an osmotic environment, and high ethanol concentration. Overcoming these limitations is critical for effective bioethanol production. In this review, the stress response mechanisms of Z. mobilis are discussed in comparison to other ethanol-producing microbes. The mechanism of stress response is divided into physiological (changes in growth, metabolism, intracellular components, and cell membrane structures) and molecular (up and down-regulation of specific genes and elements of the regulatory system and their role in expression of specific proteins and control of metabolic fluxes) changes. Systemic metabolic engineering approaches, such as gene manipulation, overexpression, and silencing, are successful methods for building new metabolic pathways. Therefore, this review discusses systems metabolic engineering in conjunction with systems biology and synthetic biology as an important method for developing new strains with an effective response mechanism to fermentation stresses during bioethanol production. Overall, understanding the stress response mechanisms of Z. mobilis can lead to more efficient and effective bioethanol production.

Graphical Abstract
Predictors of insecticide-treated bed nets use among pregnant women in Sierra Leone: evidence from the 2019 Sierra Leone Demographic Health Survey
Authors: Osborne Augustus , Bangura Camilla
Published: June 2024

Background

Malaria remains a significant public health threat in Sierra Leone, particularly for pregnant women and their unborn children. Infection during pregnancy can lead to severe consequences, including maternal anaemia, low birth weight, premature birth, and even death. Therefore, preventing malaria during pregnancy is crucial for improving maternal and child health outcomes. This study investigated the predictors of insecticide-treated bed net (ITN) use among pregnant women in Sierra Leone.

Methods

The study analysed the 2019 Sierra Leone Demographic and Health Survey data (SLDHS). The study comprised a total of 900 pregnant women aged 15–49 years, representing the nationally representative sample. A multivariable binary regression analysis was used to explore the predictors of ITN use. The regression results were presented using an adjusted odds ratio (AOR) with 95% confidence intervals (CI).

Results

The study found that the prevalence of ITN use among pregnant women was 64.2 [60.4, 67.9] in Sierra Leone. Pregnant women who were married [aOR = 2.02, 95% CI 1.32, 3.07] had higher odds of bed net use than those who were unmarried. Pregnant women with five or more children [aOR = 1.69, 95% CI 1.01, 2.84] had higher odds of mosquito bed net use than those with four and below children. Pregnant women living in the Northern, Northwestern, Southern and Western regions all had lower odds of bed net use than those in the Eastern region, with the lowest odds among those living in the western region [aOR = 0.19, 95% CI 0.09, 0.40]. Pregnant women who were Muslims [aOR = 0.63, 95% CI 0.41, 0.95] had lower odds of mosquito bed net use than Christians. Pregnant women with female household heads [aOR = 0.65, 95% CI 0.44, 0.95] had lower odds of mosquito bed net use than those with male household heads.

Conclusion

ITN use among pregnant women in Sierra Leone remains suboptimal. Marital status, parity, sex of household head, region and religion were associated with bed net use. The government and policymakers in Sierra Leone should integrate ITN education and distribution into prenatal care services, emphasizing the benefits for both mother and baby—partnering with healthcare providers to raise awareness and encourage consistent use. Involve local leaders, religious figures, and mothers' groups to promote the benefits of ITN during pregnancy. Educate husbands and partners on the importance of ITN use during pregnancy and encourage their support in its consistent use.
Providing technical assistance: lessons learned from the first three years of the WHO Adolescent and Youth Sexual and Reproductive Health and Rights Technical Assistance Coordination Mechanism
Authors: Dick Bruce , Plesons Marina , Simon Callie , Ferguson Jane , Ali Ahmed Kassem , Chandra-Mouli Venkatraman
Published: June 2024

Young people’s sexual and reproductive health (SRH) continues to be a major challenge in low and middle-income countries, with implications for public health now and in the future. Fortunately there is a growing array of evidence-based interventions, and commitments from governments, development partners and donors, to support programmes that aim to improve young people’s SRH.

However, in some situations, the technical assistance that governments feel that they need to strengthen and implement national policies and strategies, to move from words to action, is not available. The WHO Adolescent and Youth Sexual and Reproductive Health and Rights (AYSRHR) Technical Assistance (TA) Coordination Mechanism was initiated to help fill this technical assistance gap; to respond to TA requests from ministries of health in ways that are timely, efficient, effective and contribute to strengthening capacity.

This paper describes the process of developing the Technical Assistance Coordination Mechanism (TA Mechanism) and the outcomes, experiences and lessons learned after three years of working. It triangulates the findings from a preliminary review of the literature and discussions with selected key informants; the outcomes from a series of structured review meetings; and the documented processes and results of the technical assistance provided to countries.

The lessons learned focus on three aspects of the TA Mechanism. How it was conceptualized and designed: through listening to people who provide and receive AYSRHR TA and by reviewing and synthesizing past experiences of TA provision. What the TA Mechanism has achieved: a standardized process for TA provision, at different stages for a range of AYSRHR issues in ten countries in three geographic regions. And what worked well and what did not: which common challenges was the TA Mechanism able to address and which ones persisted despite efforts to avoid or resolve them. The paper ends with the implications of the lessons learned for future action.
Traditional knowledge of wild plants on traditional tools, materials, products and economic practices in southern Yemen
Authors: Al-Fatimi Mohamed
Published: June 2024

Background

The traditional knowledge in southern Yemen is rich in wild medicinal and food plants, which has been documented in our previous studies. In addition, other significant and general traditional usage for the daily livelihood requirements of local people (beyond medicinal and food plant uses) has not been studied before and needs urgent documentation.

Methods

Ethnobotanical data on of wild plants used by local people in southern Yemen were collected by oral questionnaire interviews. Most informants (n = 1020) were local elderly from 15 different localities in southern Yemen. The local names and non-medicinal and non-food uses of plants were identified and analyzed.

Results

The ethnobotanical data resulted various traditional uses of 73 plant species distributed in 28 families. The most represented families were Fabaceae, Asteraceae and Malvaceae. The most growth forms were trees and shrubs. Seven main and common categories of traditional uses were determined and classified as handicraft, health aids, livestock husbandry and beekeeping, economic and commercial plant products, agriculture tools, construction timber and fuel. The most cited species were identified for Ziziphus spina-christi, Vachellia tortilis, Vachellia nilotica, Anisotes trisulcus, Dracaena hanningtonii (Sansevieria ehrenbergii) and Aerva javanica, which have multi-purpose values of traditional usage. Nine major traditional uses of local wild plants were recorded: handicraft, agriculture tools, products aid general health, economic products, construction timber, livestock husbandry, bee keeping, fuel and ornamental.

Conclusions

Despite the challenges on local traditional knowledge of wild plants, it still requested vital to many usages of traditional life and still have an economic value and heritage required of develop the daily livelihood level of the local people especially in rural areas. This includes the traditional uses of wild plants in handicraft skills, tools of agriculture, constructions. The importance of the continuity of traditional industries and their transmission to generations lies in the local population’s reliance on local natural resources without relying on external resources in situations such as wars. This is the first study that contributes to documenting and analyzing the indigenous knowledge on traditional general usage of wild plants in southern Yemen.
Low-cost and reliable substrate-based phenotyping platform for screening salt tolerance of cutting propagation-dependent grass, paspalum vaginatum
Authors: Liu Zhiwei , Xue Wentao , Jiang Qijuan , Olaniran Ademola Olufolahan , Zhong Xiaoxian
Published: June 2024

Background

Salt tolerance in plants is defined as their ability to grow and complete their life cycle under saline conditions. Staple crops have limited salt tolerance, but forage grass can survive in large unexploited saline areas of costal or desert land. However, due to the restriction of self-incompatible fertilization in many grass species, vegetative propagation via stem cuttings is the dominant practice; this is incompatible with current methodologies of salt-tolerance phenotyping, which have been developed for germination-based seedling growth. Therefore, the performance of seedlings from cuttings under salt stress is still fuzzy. Moreover, the morphological traits involved in salt tolerance are still mostly unknown, especially under experimental conditions with varying levels of stress.

Results

To estimate the salt tolerance of cutting propagation-dependent grasses, a reliable and low-cost workflow was established with multiple saline treatments, using Paspalum vaginatum as the material and substrate as medium, where cold stratification and selection of stem segments were the two variables used to control for experimental errors. Average leaf number (ALN) was designated as the best criterion for evaluating ion-accumulated salt tolerance. The reliability of ALN was revealed by the consistent results among four P. vaginatum genotypes, and three warm-season (pearl millet, sweet sorghum, and wild maize) and four cold-season (barley, oat, rye, and ryegrass) forage cultivars. Dynamic curves simulated by sigmoidal mathematical models were well-depicted for the calculation of the key parameter, Salt50. The reliability of the integrated platform was further validated by screening 48 additional recombinants, which were previously generated from a self-fertile mutant of P. vaginatum. The genotypes displaying extreme ALN-based Salt50 also exhibited variations in biomass and ion content, which not only confirmed the reliability of our phenotyping platform but also the representativeness of the aerial ALN trait for salt tolerance.

Conclusions

Our phenotyping platform is proved to be compatible with estimations in both germination-based and cutting propagation-dependent seedling tolerance under salt stresses. ALN and its derived parameters are prone to overcome the species barriers when comparing salt tolerance of different species together. The accuracy and reliability of the developed phenotyping platform is expected to benefit breeding programs in saline agriculture.
Comparative efficacy of zero-profile implant and conventional cage-plate implant in the treatment of single-level degenerative cervical spondylosis: a systematic review and meta-analysis
Authors: Zhang Peng , Zheng Hongyu , Luo Jun , Xu Jie
Published: June 2024

Background

In recent years, the zero-profile implant (Zero-p) has emerged as a promising internal fixation technique. Although studies have indicated its potential superiority over conventional cage-plate implant (Cage-plate) in the treatment of degenerative cervical spondylosis, there remains a lack of definitive comparative reports regarding its indications, safety, and efficacy.

Methods

A computerized search was conducted on English and Chinese databases, including PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, Wanfang and VIP. Additionally, a manual search was meticulously carried out on Chinese medical journals, spanning from the inception of the respective databases until August 2023. The meta-analysis utilized a case–control study approach and was executed through the utilization of RevMan 5.3 software. Stringent quality evaluation and data extraction procedures were implemented to guarantee the reliability and validity of the findings.

Results

Nine high-quality studies with 808 patients were included. Meta-analysis showed that the operation time (MD = − 13.28; 95% CI (− 17.53, − 9.04), P < 0.00001), intraoperative blood loss (MD = − 6.61; 95% CI (− 10.47, − 2.75), P = 0.0008), incidence of postoperative dysphagia at various time points: within the first month after surgery (OR = 0.36; 95% CI (0.22, 0.58), P < 0.0001), 1–3 months after surgery (OR = 0.20; 95% CI (0.08, 0.49), P = 0.0004), the final follow-up (OR = 0.21; 95% CI (0.05, 0.83), P = 0.003) and the rate of postoperative adjacent disc degeneration (OR = 0.46; 95% CI (0.25, 0.84), P = 0.01) were significantly lower in the Zero-p group than in the Cage-plate group. Additionally, was also significantly lower in the Zero-p group. However, there were no significant differences in the JOA score, the final follow-up NDI score, surgical segmental fusion rate, postoperative height of adjacent vertebrae, or postoperative subsidence rate between the two groups.

Conclusion

In summary, when treating single-segment degenerative cervical spondylosis, both internal fixation techniques are reliable and effective. However, Zero-P  implant offer several advantages over cage-plate implant, including shorter operation duration, less intraoperative blood loss, reduced postoperative dysphagia, and slower adjacent disc degeneration. Additionally, Zero-P implant has a broader application space, making them a preferred choice in certain cases.
Evaluation of “Cognitive Behavioral Intervention for Trauma in Schools” (CBITS) in child welfare programs in Germany: study protocol of a randomized controlled trial
Authors: Pfeiffer Elisa , Dörrie Loni , Köksal Jessica , Krech Fabienne , Muche Rainer , Segler Jacob , Sachser Cedric
Published: June 2024

Background

Children and adolescents growing up in child welfare institutions have been frequently exposed to traumatic events and psychosocial stress and show elevated rates of mental disorders. Yet, there is a lack of empirically supported treatments to provide adequate mental health care for children in care suffering from trauma-related mental disorders such as posttraumatic stress disorder (PTSD), depression, and anxiety. The Cognitive Behavioral Intervention for Trauma in Schools (CBITS) is an evaluated trauma-focused cognitive-behavioral group intervention, which has proven to be effective in reducing symptoms of PTSD, depression, and anxiety for traumatized children in group settings. The trial will evaluate the effectiveness of the CBITS intervention as an outreach treatment compared with an enhanced treatment-as-usual condition (TAU +) within the German mental health and child welfare system.

Methods

In a randomized controlled trial (RCT) involving N = 90 children and adolescents, we will compare CBITS with TAU + . Participants between 8 and 16 years, reporting at least one traumatic event and moderate posttraumatic stress symptoms (PTSS), will be randomized within their child welfare institution to either one of the conditions using a CATS-2 severity-stratified block randomization. Assessments will take place at baseline, as well as 4 months and 10 months after baseline. The primary outcome is the severity of PTSS after 4 months. Secondary outcomes are depression, anxiety, irritability/anger, quality of life, and global functioning level.

Discussion

The results of our trial will provide evidence regarding effective treatment options for traumatized children in care, which represent an understudied population with limited access to mental health care. Additionally, it could serve as a blueprint for implementing trauma-focused outreach group treatments for children in care and increase the accessibility to appropriate treatment.

Trial registration

Clinical Trials.gov NCT06038357 D. September 13, 2023.
Effectiveness of repetitive transcranial magnetic stimulation for insomnia disorder on fear memory extinction: study protocol for a randomised controlled trial
Authors: Sun Jingjing , Zhang Bidan , Xu Wenyue , Li Panpan , Zhang Danwei , Zhao Bei , Wang Zhoubing , Wang Bin
Published: June 2024

Background

Fear memory extinction is closely related to insomnia. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for treating insomnia disorder (ID), and it has been shown to be an efficient method for modulating fear extinction. However, whether rTMS can improve fear extinction memory in ID patients remains to be studied. In this study, we specifically aim to (1) show that 1 Hz rTMS stimulation could improve fear extinction memory in ID patients and (2) examine whether changes in sleep mediate this impact.

Methods and design

We propose a parallel group randomised controlled trial of 62 ID participants who meet the inclusion criteria. Participants will be assigned to a real rTMS group or a sham rTMS group. The allocation ratio will be 1:1, with 31 subjects in each group. Interventions will be administered five times per week over a 4-week period. The assessments will take place at baseline (week 0), post-intervention (week 4), and 8-week follow-up (week 8). The primary outcome measure of this study will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) scores from baseline to post-intervention at week 4. The secondary outcome measures include the mean change in skin conductance response (SCR), fear expectation during fear extinction, Insomnia Severity Index (ISI), Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS).

Discussion

This study will be the first examination of the impact of rTMS on fear memory extinction in ID patients.

Trial registration

Chinese Clinical Trials Register ChiCTR2300076097. Registered on 25 September 2021.
Causality between serum uric acid and diabetic microvascular complications - a mendelian randomization study
Authors: Wu Hongli , Li Xuefeng , Zhang Wenning , Peng Huifang , Jiang Hongwei
Published: June 2024

Background

The aim of this study was to investigate whether a causal relationship exists between serum uric acid (SUA) and diabetic microvascular complications using a two-sample Mendelian randomization (MR) method.

Methods

We used the MR approach, utilizing genome-wide association study (GWAS) summary statistics, to estimate the causal effect of SUA on diabetic microvascular complications in European individuals. The summary statistical data of SUA were obtained from the open database (IEU OPEN GWAS PROJECT) (p < 5 × 10− 8), and data on diabetic microvascular complications (diabetic nephropathy, diabetic neuropathy, diabetic retinopathy) were obtained from the FinnGen consortium. F-statistics were calculated to assess the correlation between instrumental variables (IVs) and SUA, and single nucleotide polymorphisms (SNPs) associated with confounders or outcomes were excluded by consulting the PhenoScanner database. Inverse variance weighting (IVW) was used for primary estimation, and MR‒Egger, weighted median (WM), and Mendelian randomization pleiotropy residuals sum and outliers (MR-PRESSO) were used for additional assessment. Heterogeneity was assessed using the Cochran’s Q test, and polytropy was assessed using the MR‒Egger intercept.

Results

MR analysis revealed a causal relationship between a genetically predicted increase in SUA and diabetic nephropathy [OR = 1.32, 95%(CI) = 1.07–1.63, p = 0.008]. The results were consistent with those after MR-PRESSO [OR = 1.30, 95%(CI) = 1.07–1.58, p = 0.008]. There was a causal relationship between type 2 diabetes mellitus (T2DM) and renal complication IVW [OR = 1.27, 95%(CI) = 1.00–1.62, p = 0.049]. These results were consistent with those after MR-PRESSO [OR = 1.27, 95%(CI) = 1.00–1.62, p = 0.050]. There was no significant causal relationship between the genetically predicted increase in SUA and diabetic retinopathy [OR 1.09, 95%(CI) = 0.94–1.26, p = 0.249] or diabetic neuropathy [OR = 1.08, 95%(CI) = 0.84–1.40, p = 0.549].

Conclusions

This MR analysis suggests a causal relationship between genetically predicted uric acid increases and diabetic microvascular complications. A significant causal relationship exists between SUA and diabetic nephropathy but not between SUA and diabetic retinopathy or diabetic neuropathy.
Metabolomic screening of anti-inflammatory compounds in Acanthopanax sessiliflorus fruit (Ogaza) extract
Authors: Kim Gyoung-Deuck , Lee Jiho , Auh Joong-Hyuck
Published: June 2024

This study investigated the anti-inflammatory compounds in Ogaza, Acanthopanax sessiliflorus fruit, and their extracts using metabolomic screening. Ogaza extracts were obtained in various solvents, such as 70% ethanol, 70% methanol, and water. The anti-inflammatory activity was estimated by evaluating nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 cells treated with the extracts. The 70% ethanol extract (EO) showed the most effective anti-inflammatory activity, inhibiting nitric oxide production by approximately 50% and downregulating iNOS expression. The 70% ethanol extract was further fractionated into three partial subfractions by preparative LC to identify the anti-inflammatory compounds. Assessment of the anti-inflammatory activity of each subfraction revealed that the third subfraction (E-F3) showed the highest inhibitory activity against nitric oxide. E-F3 effectively suppressed iNOS expression. Subsequently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multivariate statistical analyses were performed to identify the compounds that significantly contributed to the anti-inflammatory activity of the Ogaza extract. Fourteen and 16 compounds in the negative- and positive-ion modes, respectively, were identified as significant constituents of Ogaza. Compounds like quercetin, hyperoside, acanthoside D, oleanolic acid, and scopoletin were identified as potential anti-inflammatory components in Ogaza extract. This study characterized the functional properties of Acanthopanax sessiliflorus fruit and indicated the possibility that other compartments of Acanthopanax sessiliflorus may also serve as natural sources of nutraceuticals.
Spatio-temporal evolution characteristics of cultural heritage sites and their relationship with natural and cultural environment in the northern Fujian, China
Authors: Chu Deping , Huang Chengkun , Lin Feiyang
Published: June 2024

China’s northern Fujian, as one of the spatial carriers of renowned traditional Chinese cultures such as Minyue, Zhu Xi’s Neo-Confucianism, tea, and porcelain, has preserved a wealth of tangible cultural relics, showcasing a profound cultural heritage and possessing strong research value and development potential. This study employs GIS spatial statistical analysis and map visualization technology to unveil the evolutionary processes of cultural heritage sites in northern Fujian, focusing on their spatial types, forms, and densities across different historical periods. Based on this foundation, the research further delves into the intrinsic relationships between the spatial distribution characteristics of cultural heritage sites in northern Fujian during various historical periods and the local natural and cultural environment. The results indicate that: (1) the spatial distribution of cultural heritage sites in northern Fujian varies across different historical periods, with the highest concentration and quantity observed during the Ming and Qing periods. In contrast, the Qin, Han, Wei, Jin, Northern and Southern Dynasties period exhibits the lowest quantity and a more dispersed distribution. (2) Cultural heritage sites in northern Fujian are mainly distributed in the relatively flat terrain below 400 m above sea level, including middle to low-altitude mountain basins, river valleys, and low hills. In terms of distance from rivers, cultural heritage sites exhibit a clear distribution pattern along rivers, with a large number of them located within 0–6 km from the riverbanks. (3) The spatial distribution of cultural heritage sites in northern Fujian is influenced not only by macro-environmental factors such as topography, altitude, and rivers but also by micro-shaping from social and cultural elements like Minyue culture, tea and porcelain ancient road culture, Zhu Xi’s Neo-Confucianism culture, religious beliefs and customs culture, and red revolutionary culture across different historical periods. This study contributes to the establishment of a model correlating cultural heritage sites with historical periods and provides an interdisciplinary methodological framework to understand the relationship between cultural heritage sites and the geographical environment.
Recently developed radiopharmaceuticals for bacterial infection imaging
Authors: Kahts Maryke , Summers Beverley , Gutta Aadil , Pilloy Wilfrid , Ebenhan Thomas
Published: June 2024

Background

Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019.

Main body

Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [68Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [68Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [11C]para-aminobenzoic acid and D-methyl-[11C]-methionine, with clinical trials underway for [18F]fluorodeoxy-sorbitol, as well as for 11C- and 18F-labelled trimethoprim.

Conclusion

It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors’ opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents.
Chromosome-level genome assembly provides insights into the genetic diversity, evolution, and flower development of Prunus conradinae
Authors: Jiu Songtao , Manzoor Muhammad Aamir , Chen Baozheng , Xu Yan , Abdullah Muhammad , Zhang Xinyu , Lv Zhengxin , Zhu Jijun , Cao Jun , Liu Xunju , Wang Jiyuan , Liu Ruie , Wang Shiping , Dong Yang , Zhang Caixi
Published: June 2024

Prunus conradinae, a valuable flowering cherry belonging to the Rosaceae family subgenus Cerasus and endemic to China, has high economic and ornamental value. However, a high-quality P. conradinae genome is unavailable, which hinders our understanding of its genetic relationships and phylogenesis, and ultimately, the possibility of mining of key genes for important traits. Herein, we have successfully assembled a chromosome-scale P. conradinae genome, identifying 31,134 protein-coding genes, with 98.22% of them functionally annotated. Furthermore, we determined that repetitive sequences constitute 46.23% of the genome. Structural variation detection revealed some syntenic regions, inversions, translocations, and duplications, highlighting the genetic diversity and complexity of Cerasus. Phylogenetic analysis demonstrated that P. conradinae is most closely related to P. campanulata, from which it diverged ~ 19.1 million years ago (Mya). P. avium diverged earlier than P. cerasus and P. conradinae. Similar to the other Prunus species, P. conradinae underwent a common whole-genome duplication event at ~ 138.60 Mya. Furthermore, 79 MADS-box members were identified in P. conradinae, accompanied by the expansion of the SHORT VEGETATIVE PHASE subfamily. Our findings shed light on the complex genetic relationships, and genome evolution of P. conradinae and will facilitate research on the molecular breeding and functions of key genes related to important horticultural and economic characteristics of subgenus Cerasus.
Apparent dark matter inspired by the Einstein equation of state
Authors: Jusufi Kimet , Sheykhi Ahmad
Published: June 2024

The purpose of this article is twofold. First, by means of Padmanabhan's proposal on the emergence nature of gravity, we recover the ΛCDM model and the effect of the dark matter in the context of cosmology. Toward this goal, we use the key idea of Padmanabhan that states cosmic space emerges as the cosmic time progresses and links the emergence of space to the difference between the number of degrees of freedom on the boundary and in the bulk. Interestingly enough, we show that the effect of the cold dark matter in the cosmological setup can be understood by assuming an interaction between the numbers of degrees of freedom in the bulk. In the second part, we follow Jacobson's argument and obtain the modified Einstein field equations with additional dark matter component emerging due to the interaction term between dark energy and baryonic matter related by

, where α is a coupling constant. Finally, a correspondence with the Yukawa cosmology is pointed out, and the role of massive gravitons as a possibility in explaining the nature of the dark sector as well as the theoretical origin of the Modified Newtonian Dynamics (MOND) are addressed. We speculate that the interaction coupling α fundamentally measures the entanglement between the gravitons and matter fields and there exists a fundamental limitation in measuring the gravitons wavelength.
SETD3 is a mechanosensitive enzyme that methylates actin on His73 to regulate mitochondrial dynamics and function
Authors: Deshmukh Vaibhav , Martin James F.
Published: June 2024

Mitochondria, which act as sensors of metabolic homeostasis and metabolite signaling, form a dynamic intracellular network that continuously changes shape, size and localization to respond to localized cellular energy demands. Mitochondrial dynamics and function depend on interactions with the F-actin cytoskeleton that are poorly understood. Here, we show that SET domain protein 3 (SETD3), a recently described actin histidine methyltransferase, directly methylates actin at histidine-73 and enhances F-actin polymerization on mitochondria. SETD3 is a mechano-sensitive enzyme that is localized on the outer mitochondrial membrane and promotes actin polymerization around mitochondria. SETD3 loss of function leads to diminished F-actin around mitochondria and a decrease in mitochondrial branch length, branch number and mitochondrial movement. Our functional analysis revealed that SETD3 is required for oxidative phosphorylation, and mitochondrial complex I assembly and function. Our data further indicate that SETD3 regulates F-actin formation around mitochondria and is essential for maintaining mitochondrial morphology, movement and function. Finally, we discovered that SETD3 levels are regulated by extracellular matrix (ECM) stiffness and regulate mitochondrial shape in response to changes in ECM stiffness. These findings provide new insight into the mechanism for F-actin polymerization around mitochondria.
Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease
Authors: van Keulen Anne-Marleen , Buettner Stefan , Olthof Pim B. , Klümpen Heinz-Josef , Erdmann Joris I. , Izquierdo-Sanchez Laura , Banales Jesus M. , Goeppert Benjamin , Roessler Stephanie , Zieniewicz Krzysztof , Lamarca Angela , Valle Juan W. , La Casta Adelaida , Hoogwater Frederik J. H. , Donadon Matteo , Scheiter Alexander , Marzioni Marco , Adeva Jorge , Kiudeliene Edita , Fernández Jesús María Urman , Vidili Gianpaolo , Mocan Tudor , Fabris Luca , Krawczyk Marcin , Folseraas Trine , Dopazo Cristina , Detry Olivier , Voiosu Theodor , Scripcariu Viorel , Biancaniello Francesca , Braconi Chiara , Macias Rocio I. R. , Groot Koerkamp Bas
Published: June 2024

Background

Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy.

Methods

Patients with a diagnosis of pCCA between 1997–2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS.

Results

Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55–1.07).

Conclusions

Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.
On the presence of an unexpected meadow of Penicillus capitatus Lamarck (Bryopsidales: Chlorophyta) in Mallorca, Balearic Islands, Western Mediterranean
Authors: HIERRO ANDREA , BALLESTEROS ENRIC , MAÑEZ-CRESPO JULIA , REYNÉS XESCA , TOMAS FIONA
Published: June 2024

An unexpected meadow of the warm-water alga Penicillus capitatus was found thriving in sandy bottoms between 16 and 21 m depth in Mallorca, Balearic Islands. Plant densities and benthic coverage were very high when compared to most Mediterranean meadows of this species. As it is common in tropical meadows of this species, all the individuals were found in a Penicillus morphological state, whereas most Mediterranean individuals are always found in the filamentous (Espera) state. Due to the high biomass of the populations, the contribution to the primary productivity of the sandy bottoms it colonizes should be far from negligible. If the expansion of these species continues, the annual calcium carbonate production of the Balearic continental shelf will increase and previous estimated budgets will have to be reconsidered. Since no genetic analysis of the specimens have been performed so far, it is still early to know if the studied populations have been originated by native Mediterranean specimens or from a cryptic lineage of Western Atlantic or Macaronesian origin. Whatever the answer is, the current bloom of this population in an environment completely devoid of this species in the recent past, provides new evidence of the current tropicalization of the Mediterranean caused by global warming.
Interpreting materia medica. A case study on Ioannes Archiatrus
Authors: Zipser Barbara , Lardos Andreas , Lazarou Rebecca , Allkin Robert , Nesbitt Mark , Scott Andrew C.
Published: June 2024

Background Premodern medical texts are an invaluable source for scholars from humanities and sciences. However, they are usually not accessible as few scientists with an interest in premodern materia medica are also qualiﬁed philologists. Therefore, a balance has to be struck to translate these texts while preserving information on how reliable we believe a given translation to be. In this paper, we conduct a case study on the vernacular version of Ioannes archiatrus. Methods The present study forms part of the output of a multidisciplinary Wellcome Trust Collaborative Award combining humanities and sciences. We deployed a multi-layer tagging system to systematise pharmaceutical terminology and to translate these terms while providing conﬁdence factors for individual words. In a second step, we used AntConc, a freeware concordance software, to analyse our primary source and visualise patterns in the text. Results Our methodology created a readable text that made it possible for the reader to check conﬁdence factors. It also allows our translation and tagging to be recycled for further research. Conclusions Our methods provide a tool that allows to balance the need to translate and the necessary caution about translated plant and mineral names. Our approach is transferable and it can be modiﬁed to suit the needs of other primary sources.
The genome sequence of the Common Alderfly, Sialis lutaria (Linnaeus, 1758)
Authors: Farr Andrew , Hall Daniel W. ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: June 2024

We present a genome assembly from an individual Sialis lutaria (alderfly; Arthropoda; Insecta; Megaloptera; Sialidae). The genome sequence is 462.0 megabases in span. Most of the assembly is scaffolded into 15 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.59 kilobases in length.