bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic alcohol consumption and COVID‐19 infection risk: A narrative review
Authors: Friske Marion M. , Spanagel Rainer
Published: March 2023

During the COVID‐19 pandemic, many potential risk groups have been identified, such as those with obesity, diabetes, preexisting organ injuries, and several other conditions. Smoking is the most reported substance use disorder linked to increased COVID‐19 hospitalization rate and disease severity. In relation to smoking, we discuss the impairment of the innate and the adaptive immune systems as being among the main potential reasons for increased COVID‐19 infection risk and severity. Chronic alcohol consumption and alcohol use disorder (AUD) also have a negative impact on the immune system, but when it comes to COVID‐19 risk, they produce diverse outcomes. Some studies provide evidence that chronic alcohol consumption and AUD increase the risk of COVID‐19 infection and severe disease progression, while others report reduced hospitalization and death rates. In this review, we summarize the current state of epidemiological and molecular data concerning alcohol consumption and AUD as risk factors for COVID‐19 infection, hospitalization, and mortality.
CD30‐positive lymphoproliferative disorders—An Australian Clinical Practice Statement from the Peter MacCallum Cancer Centre
Authors: Bhabha Friyana K. , McCormack Christopher , Campbell Belinda A. , Lade Stephen , Buelens Odette , Van Der Weyden Carrie , Prince H. Miles
Published: March 2023

The CD30‐postive lymphoproliferative disorders, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma, account for up to 30% of all cutaneous T‐cell lymphomas (CTCLs) and are the second most common form of CTCLs after mycosis fungoides. Both conditions differ in their clinical presentations; however, they share the expression of the CD30 antigen as a common immunophenotypic hallmark. There is a wide spectrum of management options depending on factors such as extent of disease, staging and treatment tolerability. This Clinical Practice Statement is reflective of the current clinical practice in Australia.
A study on the rapid diagnosis of chronic heart failure by measuring the difference in pulse oxygen saturation before and after arm compression
Authors: Jia Jian‐feng , Wang Li‐fei , Gao Xing‐li
Published: March 2023

Background

Clinically, the pulse oxygen saturation of patients with chronic heart failure does not decrease significantly, and the clinical manifestations of labor‐related dyspnea are not typical. As such, it is difficult to make a rapid diagnosis.

Objective

To investigate changes in pulse oxygen saturation in patients with chronic heart failure and examine the relationship between B‐type natriuretic peptide (BNP) and normal pulse oxygen saturation.

Methods

A total of 80 hospitalized patients with chronic heart failure and increased BNP were randomly selected as the study group; the family members of 60 patients without dyspnea were randomly selected as the control group. The researchers measured the value of pulse oxygen saturation before and after upper arm compression, calculating the difference and analyzing the correlation between this difference and BNP values. The data were statistically analyzed using the SPSS Statistics 17.0 program.

Results

The decrease in pulse oxygen saturation in the study group was greater than in the control group; the decrease in pulse oxygen saturation of patients with chronic heart failure positively correlated with BNP.

Conclusion

The value of pulse oxygen saturation in patients with chronic heart failure decreased more than in the control group, and this difference positively correlated with BNP. The measurement of pulse oxygen saturation before and after upper arm compression is a simple and effective method for diagnosing and evaluating chronic heart failure.
Sugar intake and colorectal cancer risk: A prospective Japanese cohort study
Authors: Kanehara Rieko , Katagiri Ryoko , Goto Atsushi , Yamaji Taiki , Sawada Norie , Iwasaki Motoki , Inoue Manami , Tsugane Shoichiro ,   JPHC Study Group
Published: March 2023

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle‐aged adults in a Japanese large‐scale population‐based cohort study. The participants (42,405 men and 48,600 women) who were 45–74 years old and answered the questionnaire in 1995–1999 in the Japan Public Health Center‐based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147‐item food frequency questionnaire and divided into quintiles (Q1–Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow‐up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07–2.87] for Q1 vs. Q5;plinear trend = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle‐aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded.
Real‐world clinical analysis in 190 advanced NSCLC patients with uncommon EGFR mutations: A multi‐center study
Authors: Qin Yi , Long Yaling , Tang Yuan , Tian Yuke , Li Juan , Duan Ping , Luo Jieyan , Yu Min , Li Yanying , Zhou Xiaojuan , Wang Ke , Gong Youling , Peng Feng , Zhu Jiang , Liu Yongmei , Zhou Lin , Lu You , Huang Meijuan
Published: March 2023

Differently from epidermal growth factor receptor (EGFR) 19Del and L858R mutations, the panoramic description of uncommon EGFR mutations is far from mature. Our understanding of its population characteristics, treatment response, and drug resistance mechanisms needs urgent expansion and deepening. Our study enrolled 437 patients with non–small‐cell lung cancer from four clinical centers and who had uncommon EGFR mutations. The clinical characteristics of all patients and the treatment outcomes of 190 advanced patients who received pharmacotherapy were analyzed. Moreover, the acquired resistance mechanisms were explored based on 53 tissue or liquid re‐biopsy data in 45 patients. Patients with EGFR 20ins had a shorter survival time compared with patients with non‐20ins mutations. In total, 149 cases had received EGFR‐tyrosine kinase inhibitors (TKI); afatinib was significantly superior to other EGFR‐TKIs both in ORR and mPFS in all uncommon mutations and especially in the L861Q group. The most common acquired drug resistance mechanism was MET amplification, followed by EGFR T790M, which was significantly different from common EGFR mutations.
tachyon: Efficient Shared Memory Parallel Computation of Extremum Graphs
Authors: Ande Abhijath , Subhash Varshini , Natarajan Vijay
Published: March 2023

The extremum graph is a succinct representation of the Morse decomposition of a scalar field. It has increasingly become a useful data structure that supports topological feature‐directed visualization of 2D/3D scalar fields, and enables dimensionality reduction together with exploratory analysis of high‐dimensional scalar fields. Current methods that employ the extremum graph compute it either using a simple sequential algorithm for computing the Morse decomposition or by computing the more detailed Morse–Smale complex. Both approaches are typically limited to two and three‐dimensional scalar fields. We describe a GPU–CPU hybrid parallel algorithm for computing the extremum graph of scalar fields in all dimensions. The proposed shared memory algorithm utilizes both fine‐grained parallelism and task parallelism to achieve efficiency. An open source software library, tachyon, that implements the algorithm exhibits superior performance and good scaling behaviour.
Esthetics and bone changes of immediate implants with or without vascularized interpositional periosteal connective tissue grafting: A 2‐year randomized controlled trial
Authors: Naiem Suzy Nabil , Hosny Manal , ElNahass Hani
Published: March 2023

Objectives

To compare esthetics at single immediately placed implants with and without soft tissue augmentation.

Materials and Methods

Patients with non‐restorable maxillary teeth in the esthetic zone were assigned into 2 groups: immediately placed implants with simultaneous vascularized interpositional periosteal connective tissue grafting (VIP‐CTG) or non‐grafted immediately placed implants (NG). The outcomes included: pink esthetic score (PES), gingival thickness, keratinized tissue width, buccal bone changes, marginal bone loss, pain, and satisfaction.

Results

Eighteen implants were included. At 2 years the mean value for PES was 12 ± 3.2 for the VIP‐CTG and 12.9 ± 1.3 for the NG (p = .855). Mucosal thickness and keratinized tissue width showed no statistically significant difference between the two groups (p = .253) and (p = .931) respectively. Clinically buccal bone showed mean bone loss of 2.03 ± 1.57 mm for VIP‐CTG and 1.09 ± 1.3 mm for NG (p = .247) and radiographically showed 1.67 ± 0.84 mm at the VIP‐CTG and 1.16 ± 0.47 mm at the NG (p = .118). No statistically significant difference between both groups was demonstrated regarding marginal bone level changes (p = .142), pain (p = .622), or satisfaction (p = .562) at any time point.

Conclusion

Simultaneous soft tissue grafting with immediate implant placement did not provide a more favorable outcome regarding esthetics or alveolar bone preservation effect. Undisturbed healing with the least surgical intervention seems to provide more favorable outcomes.
Effectiveness of modified and control protocols for the surgical therapy of combined peri‐implantitis‐related defects. A retrospective analysis
Authors: Schwarz Frank , Becker Kathrin , Albrecht Christine , Ramanauskaite Ausra , Begic Amira , Obreja Karina
Published: March 2023

Objectives

To compare the clinical effectiveness of control and two modified protocols for surgical therapy of combined peri‐implantitis‐related defects.

Materials and Methods

A total of n = 36 patients (n = 40 implants) diagnosed with combined supra‐ and intrabony defects were identified for this retrospective analysis. All protocols considered access flap surgery, granulation tissue removal and implant surface decontamination using a titanium brush. The control combined protocol included implantoplasty at supracrestal/ buccal‐ and reconstructive therapy at intrabony components using a particulate natural bone mineral + a native collagen membrane (CM) (n = 11 patients, n = 11 implants, CP). The modified protocols included the augmentation at both supra‐ and intrabony defect components using either a collagen‐stabilized natural bone mineral (BOC) (n = 15 patients, n = 15 implants, MP1), or BOC mixed with autogenous bone chips + CM (n = 10 patients, n = 14 implants, MP2). Linear mixed effects analyses were used to assess the changes in clinical parameters (i.e., bleeding on probing – BOP, probing pocket depth – PD, and mucosal recession – MR) over time (i.e., 6 and 12 months) and the impact of the treatment groups (CP, MP1, MP2).

Results

At 12 months, median BOP and PD reductions amounted to −58.33% and − 1.16 mm in the MP1, to −62.50% and −1.95 mm in the MP2, and to −66.67% and −0.83 mm in the CP groups, respectively. The associated MR changes ranged between 0.00 and 0.08 mm. The survival rates were 100% in all groups.

Conclusions

All treatment protocols were associated with short‐term improvements in the clinical parameters investigated.
Soft tissue contour changes at implant sites with or without soft tissue grafting in the esthetic zone: A retrospective case–control study with a 12‐year follow‐up
Authors: Bienz Stefan P. , Carrera Edwin Ruales , Hüsler Jürg , Roccuzzo Andrea , Jung Ronald E. , Thoma Daniel S.
Published: March 2023

Objectives

To evaluate the volumetric changes and peri‐implant health at implant sites with and without previous soft tissue grafting over a 12‐year observation period.

Materials and Methods

Eighteen patients received dental implants and simultaneously guided bone regeneration in the esthetic zone (15–25) for dental rehabilitation. Three months following implant placement, 8 patients (test) received an additional subepithelial connective tissue graft, whereas 10 patients (control) did not receive any additional treatment. One week after prothesis delivery and at the 5 and 12 years follow‐up examination, impressions were taken. Obtained casts were processed for profilometric and linear analyses. The mean distance (MD) in the mid‐buccal area between the two surfaces was considered the primary outcome. Peri‐implant health was assessed based on clinical and radiographic data.

Results

Nine female and 7 male patients were re‐assessed after a median follow‐up time of 144.5 months (Min: 114.8; Max: 213.0). The median reduction of MD amounted to −0.81 mm (Min: −1.39; Max: 0.52) in the test group and −0.56 mm (Min: −0.93; Max: 0.11) in the control group, (intergroup comparison p = .607, CI 95%: −0.760/0.530). None of the implants was diagnosed with peri‐implantitis. Six tests and two control implants were diagnosed with peri‐implant mucositis (p = .103).

Conclusions

Despite the limited number of included patients, similar results in terms of volumetric, linear changes, and peri‐implant conditions could be detected at implant sites with or without soft tissue grafting over a period of 12 years.
DNMT1 involved in the analgesic effect of folic acid on gastric hypersensitivity through downregulating ASIC1 in adult offspring rats with prenatal maternal stress
Authors: Wang Hong‐Jun , Zhang Fu‐Chao , Xu Timothy W. , Xu Yu‐Cheng , Tian Yuan‐Qing , Wu Yan‐Yan , Xu Ji‐Tian , Hu Shufen , Xu Guang‐Yin
Published: March 2023

Aims

Gastric hypersensitivity (GHS) is a characteristic pathogenesis of functional dyspepsia (FD). DNA methyltransferase 1 (DNMT1) and acid‐sensing ion channel 1 (ASIC1) are associated with GHS induced by prenatal maternal stress (PMS). The aim of this study was to investigate the mechanism of DNMT1 mediating the analgesic effect of folic acid (FA) on PMS‐induced GHS.

Methods

GHS was quantified by electromyogram recordings. The expression of DNMT1, DNMT3a, DNMT3b, and ASIC1 were detected by western blot, RT‐PCR, and double‐immunofluorescence. Neuronal excitability and proton‐elicited currents of dorsal root ganglion (DRG) neurons were determined by whole‐cell patch clamp recordings.

Results

The expression of DNMT1, but not DNMT3a or DNMT3b, was decreased in DRGs of PMS rats. FA alleviated PMS‐induced GHS and hyperexcitability of DRG neurons. FA also increased DNMT1 and decreased ASIC1 expression and sensitivity. Intrathecal injection of DNMT1 inhibitor DC‐517 attenuated the effect of FA on GHS alleviation and ASIC1 downregulation. Overexpression of DNMT1 with lentivirus not only rescued ASIC1 upregulation and hypersensitivity, but also alleviated GHS and hyperexcitability of DRG neurons induced by PMS.

Conclusions

These results indicate that increased DNMT1 contributes to the analgesic effect of FA on PMS‐induced GHS by reducing ASIC1 expression and sensitivity.
Vascular stability of brain arteriovenous malformations after partial embolization
Authors: He Yingkun , He Yanyan , Bai Weixing , Guo Dehua , Lu Taoyuan , Duan Lin , Li Zhen , Kong Lingfei , Hernesniemi Juha A. , Li Tianxiao
Published: March 2023

Introduction

Brain arteriovenous malformation (bAVM) might have a higher risk of rupture after partial embolization, and previous studies have shown that some metrics of vascular stability are related to bAVM rupture risk.

Objective

To analyze vascular stability of bAVM in patients after partial embolization.

Methods

Twenty‐four patients who underwent partial embolization were classified into the short‐term, medium‐term, and long‐term groups, according to the time interval between partial embolization and surgery. The control group consisted of 9 bAVM patients who underwent surgery alone. Hemodynamic changes after partial embolization were measured by angiogram. The inflammatory infiltrates and cell–cell junctions were evaluated by MMP‐9 and VE‐cadherin. At the protein level, the proliferative and apoptotic events of bAVMs were analyzed by immunohistochemical staining of VEGFA, eNOS, and caspase‐3. Finally, neovascularity and apoptotic cells were assessed by CD31 staining and TUNEL staining.

Results

Immediately after partial embolization, the blood flow velocity of most bAVMs increased. The quantity of MMP‐9 in the medium‐term group was the highest, and VE‐cadherin in the medium‐term group was the lowest. The expression levels of VEGFA, eNOS, and neovascularity were highest in the medium‐term group. Similarly, the expression level of caspase‐3 and the number of apoptotic cells were highest in the medium‐term group.

Conclusion

The biomarkers for bAVM vascular stability were most abnormal between 1 and 28 days after partial embolization.
Forecasting climate‐driven habitat changes for Australian freshwater fishes
Authors: Tims Amy R. , Saupe Erin E.
Published: March 2023

Aims

Climate change is expected to have profound effects on species' distributions into the future. Freshwater fishes, an important component of freshwater ecosystems, are no exception. Here, we project shifts in suitable conditions for Australian freshwater fishes under different climate change scenarios to identify species that may experience significant declines in habitat suitability.

Location

Australia.

Methods

We use MAXENT bioclimatic models to estimate the effect of climate change on the suitable conditions for 154 species of Australian freshwater fishes, of which 109 are endemic and 29 are threatened with extinction. Suitable conditions for freshwater fish species are modelled using three different Earth System climate models (ESMs) under two different emission scenarios to the year 2100. For each species, we examine potential geographic shifts in the distribution of suitable conditions from the present day to 2100 and quantify how habitat suitability may change at currently occupied sites by the end of this century.

Results

Broadscale poleward shifts in suitable conditions are projected for Australian freshwater fishes by an average of up to 0.38° (~180 km) across all species, depending on the emission scenario. Considerable loss of suitable conditions is forecast to occur within currently recognized distributional extents by 2100, with a mean projected loss of up to 17.5% across species. Predicted geographic range shifts and declines are larger under a high‐emission scenario. Threatened species are projected to be more adversely affected than nonthreatened species.

Main Conclusions

Our models identify species and geographic regions that may be vulnerable to climate change, enabling freshwater fish conservation into the future.
Effect of haemodialysis on the pharmacokinetics and pharmacodynamics of evogliptin
Authors: Kim Byungwook , Im Dha Woon , Won Heejae , Sunwoo Jung , Han Seung Seok , Lee Hajeong , Kim Dong Ki , Oh Kook‐Hwan , Joo Kwon Wook , Kim Yon Su , Cho Joo‐Youn , Lee SeungHwan , Oh Jaeseong , Jang In‐Jin , Kim Yong Chul
Published: March 2023

Aim

To investigate the possible effect of haemodialysis (HD) on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor.

Methods

A single‐dose, open‐label, parallel‐group study of eight end‐stage renal disease (ESRD) patients and eight matched healthy subjects was conducted. ESRD patients received a single oral dose of evogliptin 5 mg after and before HD with a 2‐week washout between each dose, and healthy subjects received a single oral dose of evogliptin 5 mg. Serial blood, dialysate, and urine samples were collected to assess the PK and PD profiles of evogliptin. To compare PK parameters before and after HD, geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated.

Results

The GMRs for the maximum concentration and area under the concentration‐time curve from time 0 to the last measurable timepoint (AUClast) of evogliptin when administered before HD compared with after HD were 0.7293 (90% CI 0.6171‐0.8620) and 0.9480 (90% CI 0.8162‐1.1010), respectively. The maximum DPP‐4 inhibitory effect, area under the DPP‐4 inhibitory effect‐time curve, and time duration of more than 80% DPP‐4 inhibition were comparable when evogliptin was administered before and after HD. Compared with healthy subjects, the mean AUClast of evogliptin was approximately 1.4‐fold greater in ESRD patients, but the difference is unlikely to affect the safety and efficacy of evogliptin.

Conclusion

The effect of HD on the PK and PD characteristics of evogliptin was not clinically significant; therefore, dose adjustment according to HD status is not necessary.
Termite exocrine systems: a review of current knowledge
Authors: Costa‐Leonardo Ana Maria , da Silva Iago Bueno , Laranjo Lara Teixeira
Published: March 2023

In this review, we summarize the 22 exocrine glands hitherto described for termites (Isoptera), highlighting their distribution, morphological features, and likely function. The secretion from such glands displays a very important role in termite communication, but is also attributed to many other activities performed by these insects, including defense, building, and foraging, as well as physiological processes such as the synthesis of digestive enzymes, and antiseptic and lubricant compounds. Here, glands are divided into those associated with termite mouthparts and other head appendages, tegumentary glands with epithelial arrangement, those related to the reproductive apparatus, and glands which do not fit into these divisions. The exocrine systems in termites may be composed of classes 1, 2, and 3 secretory cells, which differ in how the glandular secretion is released. Moreover, they may exhibit a varied composition of secretory cell classes. Different glands may be involved in specific tasks and therefore produce specific compounds, although there are cases in which the same content is secreted by different glands, suggesting a functional plasticity. The chemical nature of these secretions and their role are well known for some glands, such as the frontal, salivary, tergal, and sternal ones. On the other hand, such aspects remain speculative or completely unknown for other glands. The number of termite exocrine glands is extremely low when compared to those described for eusocial Hymenoptera, and is a likely consequence of the higher diversity of species and chemical communication in the latter group. Moreover, vibroacoustic signals represent an important type of communication in termites. Further studies are encouraged to provide new insights into the occurrence and function of the exocrine systems in termites and how they modulate the different activities displayed by them.
Occurrence of Phytophthora species in riparian stands of black alder (Alnus glutinosa) in Slovakia
Authors: Tkaczyk Miłosz , Sikora Katarzyna , Galko Juraj , Kunca Andrej
Published: March 2023

During the monitoring period of alder decline phenomenon in Slovakia, indicative symptoms of Phytophthora diseases were observed in riverside stands in Slovakia. The study aimed to test the presence and diversity of Phytophthora species in declining alder stands. The samples were collected from six stands situated by rivers/streams in the central and eastern parts of Slovakia. Phytophthora plurivora and P. cactorum were detected in soil, root and water samples. The most isolated species was P. plurivora. Both Phytophthora species have been recognized in the literature as the perpetrators of black alder dieback together with other species, such as P. alni or P. polonica. To our knowledge, this is the first report of P. plurivora and P. cactorum in riverside stands with the main share of black alder in Slovakia.
The role of soft law in advancing the rights of persons with disabilities in the EU: A ‘hybridity’ approach to EU disability law
Authors: Ferri Delia
Published: March 2023

This article discusses the role of soft law in advancing the rights of persons with disabilities in the European Union (EU). In doing so, it revisits the emergence of the standalone, yet cross‐cutting, field of ‘EU disability law’ through the lens of the ‘hybridity theory’ advanced inter alia by Trubek and Trubek. Being speculative in nature, this article construes EU disability law as a fruitful area for an enquiry into the dynamic relationship between hard and soft law. Until the entry into force of the Treaty of Amsterdam, soft law was crucial to attract disability within the sphere of action of the EU and to embed the social model of disability, displaying a value‐setting role. In the post‐Amsterdam period, soft law and hard law coexisted, being complementary to one another. Both contributed to a common objective, namely that of advancing equality of opportunities for persons with disabilities. After the conclusion of the UN Convention on the Rights of Persons with Disabilities, the dynamic relationship between hard and soft law has become more complex and akin to what Trubek and Trubek define as ‘transformation’.
A screen for histone mutations that affect quiescence in S. cerevisiae
Authors: Small Eric M. , Osley Mary Ann
Published: March 2023

Quiescence or G0 is a reversible state in which cells cease division but retain the ability to resume proliferation. Quiescence occurs in all organisms and is essential for stem cell maintenance and tissue renewal. It is also related to chronological lifespan (CLS)—the survival of postmitotic quiescent cells (Q cells) over time—and thus contributes to longevity. Important questions remain regarding the mechanisms that control entry into quiescence, maintenance of quiescence and re‐entry of Q cells into the cell cycle. S. cerevisiae has emerged as an excellent organism in which to address these questions because of the ease in which Q cells can be isolated. Following entry into G0, yeast cells remain viable for an extended period and can re‐enter the cell cycle when exposed to growth‐promoting signals. Histone acetylation is lost during the formation of Q cells and chromatin becomes highly condensed. This unique chromatin landscape regulates quiescence‐specific transcriptional repression and has been linked to the formation and maintenance of Q cells. To ask whether other chromatin features regulate quiescence, we conducted two comprehensive screens of histone H3 and H4 mutants and identified mutants that show either altered quiescence entry or CLS. Examination of several quiescence entry mutants found that none of the mutants retain histone acetylation in Q cells but show differences in chromatin condensation. A comparison of H3 and H4 mutants with altered CLS to those with altered quiescence entry found that chromatin plays both overlapping and independent roles in the continuum of the quiescence program.
An anti‐leishmanial compound 4′,7‐dihydroxyflavone elicits ROS‐mediated apoptosis‐like death in Leishmania parasite
Authors: Sasidharan Santanu , Saudagar Prakash
Published: March 2023

The treatment for leishmaniasis is currently plagued by side effects such as toxicity and the emergence of drug resistance to the available repertoire of drugs, as well as the expense of these drugs. Considering such rising concerns, we report the anti‐leishmanial activity and mechanism of a flavone compound 4′,7‐dihydroxyflavone (TI 4). Four flavanoids were initially screened for anti‐leishmanial activity and cytotoxicity. The results showed that the compound TI 4 exhibited higher activity and selectivity index at the same time as maintaining low cytotoxicity. Preliminary microscopic studies and fluorescence‐activated cell sorting analysis reported that the parasite underwent apoptosis on TI 4 treatment. Further in‐depth studies revealed high reactive oxygen species (ROS) production and thiol levels in the parasites, suggesting ROS‐mediated apoptosis in the parasites upon TI 4 treatment. Other apoptotic indicators such as intracellular Ca2+ and mitochondrial membrane potential also indicated the onset of apoptosis in the treated parasites. The mRNA expression levels signified that the redox metabolism genes were upregulated by two‐fold along with the apoptotic genes. In summary, the use of TI 4 on Leishmania parasites induces ROS‐mediated apoptosis; therefore, the compound has immense potential to be an anti‐leishmanial drug. However, in vivo studies would be required to ascertain its safety and efficacy before we can exploit the compound against the growing leishmaniasis crisis.
Bioavailability of mineral‐associated trace metals as cofactors for nitrogen fixation by Azotobacter vinelandii
Authors: Srivastava Shreya , Dong Hailiang , Baars Oliver , Sheng Yizhi
Published: March 2023

Life on Earth depends on N2‐fixing microbes to make ammonia from atmospheric N2 gas by the nitrogenase enzyme. Most nitrogenases use Mo as a cofactor; however, V and Fe are also possible. N2 fixation was once believed to have evolved during the Archean‐Proterozoic times using Fe as a cofactor. However, δ15N values of paleo‐ocean sediments suggest Mo and V cofactors despite their low concentrations in the paleo‐oceans. This apparent paradox is based on an untested assumption that only soluble metals are bioavailable. In this study, laboratory experiments were performed to test the bioavailability of mineral‐associated trace metals to a model N2‐fixing bacterium Azotobacter vinelandii. N2 fixation was observed when Mo in molybdenite, V in cavansite, and Fe in ferrihydrite were used as the sole sources of cofactors, but the rate of N2 fixation was greatly reduced. A physical separation between minerals and cells further reduced the rate of N2 fixation. Biochemical assays detected five siderophores, including aminochelin, azotochelin, azotobactin, protochelin, and vibrioferrin, as possible chelators to extract metals from minerals. The results of this study demonstrate that mineral‐associated trace metals are bioavailable as cofactors of nitrogenases to support N2 fixation in those environments that lack soluble trace metals and may offer a partial answer to the paradox.
Tongue training technique for guiding the mandible in establishing horizontal jaw relation in edentulous patients
Authors: Singarvel Chidambaranathan Ahila , Madan Vidhya , Balasubramanium Muthukumar
Published: March 2023

Background

Edentulous patients have poor neuromuscular proprioception to guide the mandible to the desirable horizontal relation. Horizontal jaw relation is a complex relationship in which variation may occur in vertical, anteroposterior and mediolateral directions.

Objective

The aim of this study was to train the tongue and bring the mandible to centric relation in geriatric edentulous cases.

Materials and Methods

Protrude the tongue to the maximum length and retract back to centric relation, move the tongue on the left side beyond the angle of the mouth and bringing back to centric relation, move the tongue on the right and left side beyond the angle of the mouth and bringing back to centric relation, then the tongue should move upwards and touches the marginal tubercle of upper lip and bringing back to centric relation and move the tongue upward and posteriorly to touch the posterior part of the hard palate of the maxilla and swallowing.

Results

Edentulous patient can successfully move the mandible in centric relation after training the tongue.

Conclusion

The present technique is useful for establishment of horizontal jaw relation in edentulous cases using tongue training exercise in Prosthodontic dentistry.
Regulation mechanisms of CARMA1–Bcl10–MALT1 complex assembly inferred from the analysis of TRAF6‐deficient cells
Authors: Inoue Kentaro , Yasuda Tomoharu , Baba Yoshihiro , Yamamoto Tadashi , Kurosaki Tomohiro , Shinohara Hisaaki
Published: March 2023

The CARMA1–Bcl10–MALT1 (CBM) signalosome is a crucial module of NF‐κB activation in B cell receptor (BCR) signaling. Biophysical studies have shown that the E3 ubiquitin ligase TRAF6 cooperatively modifies the CBM signalosome; however, the specific details regarding how TRAF6 is involved in BCR signal‐induced CBM formation remain unclear. In this study, we aimed to reveal the influences of TRAF6 on CBM formation and TAK1 and IKK activities using DT40 B cells which lack all the exons of TRAF6. In TRAF6‐null cells we found: (i) attenuation of TAK1 activity and abolishment of IKK activity and (ii) sustained binding of CARMA1 to Bcl10. To account for the molecular mechanism causing these dynamics, we performed a mathematical model analysis. The mathematical model analysis showed that the regulation of IKK activation by TRAF6 can reproduce TAK1 and IKK activities in TRAF6 null cells, and that the TRAF6 related signal‐dependent inhibitor suppresses CARMA1 binding to Bcl10 in wild‐type cells. These results suggest that TRAF6 contributes to the positive regulation of IKK activation via TAK1, alongside the negative signal‐dependent regulation of CARMA1 binding to Bcl10.
Femme‐toring: Leveraging critical femininities and femme theory to cultivate alternative approaches to mentoring
Authors: Hoskin Rhea Ashley , Whiley Lilith A.
Published: March 2023

Both traditional and new‐wave mentoring (or men‐toring), intentionally or unintentionally, maintain and reproduce neoliberal toxic masculinist norms in academia. By applying femme theory and critical femininities frameworks, we expose how men‐toring is exclusionary and assimilationist. We then queer and feminize mentoring, developing femme‐toring as an alternative reformist approach rooted in fem(me)inist epistemologies and ethics of care, in particular, softness, vulnerability, collaboration, and yielding. Leveraging systems theory and Foucauldian theory, we contend that by centering femininity in these ways, femme‐toring unsettles toxic masculinist norms and offers possibilities for a more inclusive academia.
Acceptability of risk stratification within population‐based cancer screening from the perspective of the general public: A mixed‐methods systematic review
Authors: Taylor Lily C. , Hutchinson Alison , Law Katie , Shah Veeraj , Usher‐Smith Juliet A. , Dennison Rebecca A.
Published: March 2023

Introduction

Risk‐stratified cancer screening has the potential to improve resource allocation and the balance of harms and benefits by targeting those most likely to benefit. Public acceptability has implications for engagement, uptake and the success of such a programme. Therefore, this review seeks to understand whether risk stratification of population‐based cancer screening programmes is acceptable to the general public and in what context.

Methods

Four electronic databases were searched from January 2010 to November 2021. Qualitative, quantitative and mixed‐methods papers were eligible for inclusion. The Joanna Briggs Institute convergent integrated approach was used to synthesize the findings and the quality of included literature was assessed using the Mixed Methods Appraisal Tool. The Theoretical Framework of Acceptability was used as a coding frame for thematic analysis. PROSPERO record 2021 CRD42021286667.

Results

The search returned 12,039 citations, 22 of which were eligible for inclusion. The majority of studies related to breast cancer screening; other cancer types included ovarian, kidney, colorectal and prostate cancer. Risk stratification was generally acceptable to the public, who considered it to be logical and of wider benefit than existing screening practices. We identified 10 priorities for implementation across four key areas: addressing public information needs; understanding communication preferences for risk estimates; mitigating barriers to accessibility to avoid exacerbating inequalities; and the role of healthcare professionals in relation to supporting reduced screening for low‐risk individuals.

Conclusion

The public generally find risk stratification of population‐based cancer screening programmes to be acceptable; however, we have identified areas that would improve implementation and require further consideration.

Patient or Public Contribution

This paper is a systematic review and did not formally involve patients or the public; however, three patient and public involvement members were consulted on the topic and scope before the review commenced.
Mitochondria‐associated endoplasmic reticulum membrane: Overview and inextricable link with cancer
Authors: Yang Xi , Zhuang Jing , Song Weilong , Shen Wangjie , Wu Wei , Shen Hong , Han Shuwen
Published: March 2023

The mitochondrial‐associated membrane (MAM) is a physical platform that facilitates communication between the endoplasmic reticulum (ER) and mitochondria. It is enriched with many proteins and enzymes and plays an important role in the regulation of several fundamental physiological processes, such as calcium (Ca2+) transfer, lipid synthesis, cellular autophagy and ER stress. Accumulating evidence suggests that oncogenes and suppressor genes are present at the ER‐mitochondrial contact site, and their alterations can affect Ca2+ flux, lipid homeostasis, and the dysregulation of mitochondrial dynamics, thereby influencing the fate of cancer cells. Understanding the fundamental role of MAM‐resident proteins in tumorigenesis could support the search for novel therapeutic targets in cancer. In this review, we summarize the basic structure of MAM and the core functions of MAM‐resident proteins in tumorigenesis. In addition, we discuss the mechanisms by which natural compounds promote cancer cell apoptosis from the perspective of ER stress.
Tumour suppressor PTEN activity is differentially inducible by myo‐inositol phosphates
Authors: Grzymajlo Krzysztof , El Hafny‐Rahbi Bouchra , Kieda Claudine
Published: March 2023

Tumour evolution and efficacy of treatments are controlled by the microenvironment, the composition of which is primarily dependent on the angiogenic reaction to hypoxic stress. Tumour angiogenesis normalization is a challenge for adjuvant therapy strategies to chemo‐, radio‐ and immunotherapeutics. Myo‐inositol trispyrophosphate (ITPP) appears to provide the means to alleviate hypoxia in the tumour site by a double molecular mechanism. First, it modifies the properties of red blood cells (RBC) to release oxygen (O2) in the hypoxic sites more easily, leading to a rapid and stable increase in the partial pressure of oxygen (pO2). And second, it activates the endothelial phosphatase and tensin homologue deleted on Chromosome 10 (PTEN). The hypothesis that stable normalization of the vascular system is due to the PTEN, a tumour suppressor and phosphatase which controls the proper angiogenic reaction was ascertained. Here, by direct biochemical measurements of PTEN competitive activity in relation to PIP2 production, we show that the kinetics are complex in terms of the activation/inhibition effects of ITPP with an inverted consequence towards the kinase PI3K. The use of the surface plasmon resonance (SPR) technique allowed us to demonstrate that PTEN binds inositol derivatives differently but weakly. This method permitted us to reveal that PTEN is highly sensitive to the local concentration conditions, especially that ITPP increases the PTEN activity towards PIP3, and importantly, that PTEN affinity for ITPP is considerably increased by the presence of PIP3, as occurs in vivo. Our approach demonstrates the validity of using ITPP to activate PTEN for stable vessel normalization strategies.
Narrative review of ferroptosis in obesity
Authors: He Lian‐Ping , Zhou Zi‐Xuan , Li Cui‐Ping
Published: March 2023

Obesity is widely recognized as a major global health problem caused by a chronic energy imbalance resulting from a combination of excess caloric intake and insufficient energy expenditure. Excessive energy intake and physical inactivity are traditional risk factors for obesity. Obesity is a risk factor for many diseases, including hypertension, diabetes and tumours. Recent studies have found a strong link between ferroptosis and obesity. Ferroptosis is an iron‐dependent regulated cell death caused by iron overload and reactive oxygen species‐dependent excessive accumulation of lipid peroxidation. Ferroptosis is involved in many biological processes, such as amino acid metabolism, iron metabolism and lipid metabolism. Some potential strategies to reduce the adverse effects of ferroptosis on obesity are suggested and future research priorities are highlighted.
Association between equol producers and type 2 diabetes mellitus among Japanese older adults
Authors: Hamaura Kiho , Murakami Hiroshi , Tamura Ayumi , Matsuki Kota , Sato Eri , Tanabe Jutaro , Yanagimachi Miyuki , Oishi Maika , Iino Kaori , Okuyama Shinya , Mikami Tatsuya , Ueno Tomomi , Uchiyama Shigeto , Yokoyama Yoshihito , Daimon Makoto
Published: March 2023

Aims/Introduction

Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non‐producers and type 2 diabetes.

Materials and Methods

The participants included 147 patients with type diabetes mellitus aged 70–89 years, and 147 age‐ and sex‐matched controls. To ascertain the equol producers or non‐producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut‐off value −1.75).

Results

The urinary equol concentration was significantly lower in the diabetes group compared with the non‐diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non‐diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non‐diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non‐equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01).

Conclusions

Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia.
Signaling pathways that regulate adaptive β‐cell proliferation for the treatment of diabetes
Authors: Shirakawa Jun
Published: March 2023

The decline in β‐cell mass due to the failure of β‐cell compensation is one cause of the development of type 2 diabetes. Therefore, elucidation of the mechanism by which an adaptive increase in β‐cell mass occurs in vivo will lead to the development of a cure for diabetes. Insulin and insulin receptor (IR)‐mediated signaling pathways play an important role in the mechanism that increases β‐cell mass by compensatory β‐cell proliferation in response to chronic insulin resistance. However, whether IR is required for compensatory β‐cell proliferation remains controversial in some situations. It might be possible that IR acts as a scaffold for the signaling complex independent of its ligand. It has also been reported that the forkhead box protein M1/polo‐like kinase 1/centromere protein A pathway plays a central role in adaptive β‐cell proliferation during diet‐induced obesity, hyperglycemia, pregnancy, aging and acute insulin resistance. We recently reported that the cross‐talk of islets with fat tissue, in addition to the liver, through humoral factors is involved in adaptive β‐cell proliferation. This accommodative response of β‐cell proliferation through adipocytes was observed particularly under an acute insulin resistance state in an IR/insulin signal‐independent and forkhead box protein M1/polo‐like kinase 1/centromere protein A pathway‐dependent manner. A remaining barrier for the treatment of human diabetes using β‐cells is the differences between human and rodent islets. In this review, the focus is on signaling pathways that regulate adaptive β‐cell proliferation for the treatment of diabetes considering the abovementioned issues.
Effect of a reused insulin needle remaining in a patient's body
Authors: Qiao Yong‐jie , Xin‐yuan Yu , Xu Rui‐ling , Song Xiao‐yang , Ye Shuo , Zhen Ping , Zhou Sheng‐hu , Zhang Hao‐qiang
Published: March 2023

Diabetes is one of the most common chronic diseases at present, and insulin pen injection therapy plays an important role in the treatment of diabetes. However, the majority of patients might reuse disposable insulin pen needles for various reasons, which leads to related complications. As far as we know, this article is the first to describe a patient whose needle remained in the right upper limb while reusing a disposable insulin injection needle for subcutaneous insulin injection with the non‐dominant hand. The patient went to the doctor 1 week later. The needle moved from the lateral area of the proximal upper arm (the injection site) to the posterolateral area of the distal upper arm. The needle was then successfully removed by surgery. The reuse of disposable insulin pen needles might lead to serious complications. It is suggested to strengthen the education of people living with diabetes to help them use insulin pen needles safely.
Comparison of the minimally‐invasive roll‐in envelope flap technique to the holding suture technique in implant surgery: A prospective case series
Authors: Shakibaie Behnam , Sabri Hamoun , Blatz Marcus B. , Barootchi Shayan
Published: March 2023

Objecive

The peri‐implant soft tissue phenotype plays a role in the long‐term success of dental implants, thus, creating the need for the application of different techniques for the management of its adjacent soft tissues. The aim of this case series was to describe and evaluate the clinical outcomes of the microsurgical roll‐in‐envelope flap (RIE) approach, in comparison with a more commonly used method for manipulation of the peri‐implant soft tissues, namely the holding‐suture flap (HS) technique.

Materials and Methods

10 posterior dental implants in 10 healthy individuals were selected and randomly assigned treatment by each of the mentioned groups relative to the flap design. Mucosal thickness was measured at the time of the surgery and at 6 and 12 weeks, serving as the main outcome.

Results

The healing was uneventful at all sites without any patient drop‐outs. The comparison of two groups revealed a three‐fold reduction in the mucosal thickness in HS group compared to RIE.

Conclusions

In presence of sufficient periimplant supporting tissues and when indicated, the RIE flap seems to yield superior outcomes reducing pain/discomfort compared to connective tissue grafts.