bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune disturbances in female genital tuberculosis and latent genital tuberculosis
Authors: Sharma Jai Bhagwan , Sharma Sangeeta , Sharma Eshani , Dharmendra Sona , Singh Sheena
Published: December 2022

Background

Female genital tuberculosis (FGTB), an important clinical sub‐type of extra‐pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity.

Aims

This review tries to elucidates the role of various immune factors in FGTB and LGTB.

Content

Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa‐B (NF‐KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti‐tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in‐vitro fertilization and embryo transfer may be required for some women.

Implications

Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.
Chlamydia trachomatis antigen induces TLR4‐TAB1‐mediated inflammation, but not cell death, in maternal decidua cells
Authors: Ortiz Briana , Driscoll Ashley , Menon Ramkumar , Taylor Brandie D. , Richardson Lauren S.
Published: December 2022

Background

During gestation, the decidua is an essential layer of the maternal‐fetal interface, providing immune support and maintaining inflammatory homeostasis. Although Chlamydia (C.) trachomatis is associated with adverse pregnancy outcomes the pathogenic effects on maternal decidua contributing to adverse events are not understood. This study examined how C. trachomatis antigen affects cell signaling, cell death, and inflammation in the decidua.

Methods

Primary decidua cells (pDECs) from term, not‐in‐labor, fetal membrane‐decidua were cultured using the following conditions: (1) control – standard cell culture conditions, (2) 100 ng/ml or (3) 200 ng/ml of C. trachomatis antigen to model decidual cell infection in vitro. Differential expression of Toll‐like receptor (TLR) 4 (receptor for C. trachomatis antigen), signaling pathway markers phosphorylated TGF‐Beta Activated Kinase 1 (PTAB1), TAB1, phosphorylated p38 mitogen‐activated protein kinases (Pp38 MAPK), and p38 MAPK (western blot), decidual cell apoptosis and necrosis (flow cytometry), and inflammation (ELISA for cytokines) were determined in cells exposed to C. trachomatis antigen. T‐test was used to assess statistical significance (p < 0.05).

Results

C. trachomatis antigen significantly induced expression of TLR4 (p = 0.03) and activation of TAB1 (p = 0.02) compared to controls. However, it did not induce p38 MAPK activation. In addition, pDECs maintained their stromal cell morphology when exposed to C. trachomatis antigen showing no signs of apoptosis and/or necrosis but did induce pro‐inflammatory cytokine interleukin (IL)‐6 (100 ng/ml: p = 0.02 and 200 ng/ml: p = 0.03), in pDECs compared to controls.

Conclusion

Prenatal C. trachomatis infection can produce antigens that induce TLR4‐TAB1 signaling and IL‐6 inflammation independent of Pp38 MAPK and apoptosis and necrosis. This suggests that C. trachomatis can imbalance decidual inflammatory homeostasis, potentially contributing to adverse events during pregnancy.
Does milk of magnesia impact length of hospital stay after major colorectal resection
Authors: Tatar Cihad , Hinckley Sam , Holubar Stefan D. , Liska David , Delaney Conor P. , Steele Scott R. , Gorgun Emre
Published: December 2022

Backgrounds

Milk of magnesia (MoM) has been reported to accelerate return of bowel function following surgery. However, there is insufficient evidence regarding the impact of MoM on postoperative recovery after colorectal surgery. We aimed to determine the impact of MoM on postoperative length of stay in patients undergoing colorectal surgery.

Methods

All patients who underwent colorectal resection without an ileostomy between 2015 and 2018 were included. Patients were divided into two groups based on whether postoperative MoM (MoM) was administered or not, according to surgeons' prescribing preferences. Consecutive patients of surgeons who prescribe MoM were included in the MoM group, while consecutive patients of surgeons who prefer not to prescribe MoM served as the control group. Age, gender, preoperative comorbidities, surgical approach, length of stay, readmission, postoperative complications and mortality were evaluated and compared between the groups.

Results

A total of 3292 patients were included; 523 (15.9%) patients were prescribed MoM. Patients in the MoM group were found to be significantly older, with higher BMI and ASA class, and more often undergoing operations for cancer resection or colostomy creations, than the control group. Postoperative complications were comparable between the groups. On multivariable linear regression, MoM use was associated with a 14.1% reduction in length of stay (MoM group 4 (2; 8), control group 5 (3; 8 P = 0.006)).

Conclusion

MoM as adjunct medication in the postoperative period following colorectal surgery is associated with reduced length of stay, without an increase in postoperative complications.
Detection of physiological control inputs preload and afterload from intrinsic pump parameters in total artificial heart
Authors: Kirn Borut , Diedrich Mario , Schmitz‐Rode Thomas , Steinseifer Ulrich , Jansen Sebastian V.
Published: December 2022

Background

In the total artificial heart (TAH), the inputs to the physiological control unit, preload, and afterload, are detected from intrinsic pump parameters (e.g., motor current). Within this study, their detection techniques are developed, and their reliability in pre‐ and afterload prediction is mapped for a broad range of cardiovascular system states.

Methods

We used ReinHeart TAH which is a fully implantable TAH with a plunger coil drive that is alternately emptying the left and right chambers. From the coil currents we first derived a force generated by the piston with respect to its position and then analyzed its pattern to detect (1) preload—chamber filling, found as piston position at begin ejection and (2) afterload—mean outflow pressures, determined as linearly calibrated average piston force during ejection. TAH is then integrated into a mock loop circulation (MLC) which is set to 135 different steady operating points varying in chamber filling (0%–100%, five steps), mean outflow pressures (system circulation: 60–90–120 mm Hg, pulmonary circulation: 15–30‐45 mm Hg), and heart cycle duration (171–600 ms in seven non‐equidistant steps). The detected preload and afterload are compared to MLC set values, and the errors are mapped.

Results

Respectively for the left and right chambers, the preload was detectable in 134 and 118 operating points and the mean error was ±3% and ±2%. The afterload was detectable in 135 and 87 operating points and the mean error was 37% and 30% respectively for left and right circulation. The operational points that are further away from homeostatic equilibrium values generally yielded larger errors. The largest errors were observed for right circulation at long cycle duration, low afterload, and low filling.

Conclusions

The study yields reliable preload estimation in a broad range of physiological states, particularly for left circulation. Detection of afterload needs further improvements. The study revealed a need for piston movement optimization within the ReinHeart TAH during the early phase of systole.
Faecal microbiota transplantation for recurrent C. difficile infections: challenges and improvement opportunities for clinical practice and healthcare systems
Authors: Hocking Lucy , Ianiro Gianluca , Leong Rupert W. , Iqbal Tariq , Kao Dina , Cabling Mark , Stockwell Stephanie , Romanelli Robert J. , Marjanovic Sonja
Published: December 2022

Background

There is growing interest in faecal microbiota transplantation (FMT) as a treatment for recurrent Clostridioides difficile infection (CDI), but evidence on the diverse requirements for safe, effective and accessible services is fragmented and limited.

Aims

To identify key components of FMT provision relating to the patient care pathway, stool donor pathway and wider healthcare system, and to explore variation in practice

Methods

We conducted a narrative review of the literature and consultations with key clinical experts in the field. Evidence is drawn from high‐income country contexts, with an emphasis on Australia, Canada, Italy and the United Kingdom as case example countries.

Results

We identify and discuss key challenges to do with healthcare capacity (workforce, FMT and stool banking facilities), donors and donations, patient access and choice of FMT delivery routes, regulation, costs and reimbursement. We also identify improvement opportunities to increase awareness of FMT and referral processes, physician training, maintaining patient registries and outcome monitoring metrics, in‐country regulatory harmonisation and tackling reimbursement challenges and discuss future research needs.

Conclusion

Effectively bringing FMT to patients in a healthcare system requires much more than just the existence of a clinically effective procedure. With FMT being a potentially effective treatment option for recurrent CDI for many patients, a well‐rounded understanding of how appropriate FMT capacity can be built and nurtured is important for both healthcare providers and policymakers seeking to improve patient care.
Effectiveness of organizational interventions on appropriate opioid prescribing for noncancer pain upon hospital discharge: A systematic review
Authors: Phinn Katelyn , Liu Shania , Patanwala Asad E. , Penm Jonathan
Published: December 2022

This study aims to summarize the effectiveness of organizational interventions on appropriate opioid prescribing for noncancer pain upon hospital discharge. A systematic search was conducted on 6 electronic databases by 2 independent reviewers. We included original research articles reporting on quantitative outcomes of organizational interventions targeting appropriate opioid prescribing on hospital discharge. Quality assessment was performed by 2 independent reviewers. The protocol for this review was prospectively registered on PROSPERO (ID: CRD42020156104). Out of 173 full texts assessed for eligibility, 43 were included in this review. The majority of studies had a moderate to serious risk of bias (33 out of 43). Most of the studies implemented a multifaceted organizational intervention (16 studies). Other interventions included guideline implementation, prescriber education and default opioid‐prescribing quantity changes in electronic medical records. Multiple studies found that the dissemination of patient‐specific and procedure‐specific guidelines reduced the quantity of opioids prescribed by 44 to 57%. Prescriber education provided with feedback was implemented in 4 studies and resulted in a 33 to 44% decrease in prescribing rates. Lowering the default quantities in the electronic medical records produced a 40% decrease in opioids prescribed in 1 study. Guideline implementation, prescriber education and default opioid‐prescribing quantity changes all appear effective in improving the appropriate prescribing of opioids on hospital discharge. However, the extent of reduction of opioid prescribing upon hospital discharge after the implementation of multifaceted intervention strategies appears similar to that of simpler interventions which require fewer resources.
A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease
Authors: Gamez Josep , Calopa Matilde , Muñoz Esteban , Ferré Aileen , Huertas Oscar , McAllister Kevin , Reig Núria , Scart‐Grès Catherine , Insa Raúl , Kulisevsky Jaime
Published: December 2022

Aims

The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β1‐adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD).

Methods

A randomized, placebo‐controlled proof‐of‐concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6‐week periods each. Patients received placebo and SOM3355 at 100 and 200 mg twice daily in a crossover design. The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period.

Results

The primary endpoint was met in 57.1% of the patients. Improvements ≥3, ≥4, ≥5 and ≥6 points vs. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed‐model analysis found a significant improvement in the total maximal chorea score of −1.14 (95% confidence interval, −2.11 to −0.16; P = .0224) with 200 mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7–1.9‐fold was recorded (P < .005), probably reflecting the effect on the dopamine pathway, consistent with vesicular monoamine transporter type 2 inhibition. The most frequent adverse events during SOM3355 administration were mild to moderate.

Conclusion

Within the limits of this study, the results suggest that SOM3355 reduces chorea in patients with HD and is well‐tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug.

EudraCT number: 2018–000203‐16 and ClinicalTrials.gov Identifier: NCT03575676.
Time‐to‐event surrogate end‐points in multiple myeloma randomised trials from 2005 to 2019: A surrogacy analysis
Authors: Etekal Tommy , Koehn Kelly , Sborov Douglas W. , McClune Brian , Prasad Vinay , Haslam Alyson , Berger Katherine , Booth Christopher , Al Hadidi Samer , Abdallah Al‐Ola , Goodman Aaron , Mohyuddin Ghulam Rehman
Published: December 2022

Use of surrogate end‐points such as progression‐free survival (PFS) and other time‐to‐event (TTE) end‐points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end‐points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co‐primary end‐point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38–0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30–0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42–0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.
Median 5‐year outcomes of primary focal irreversible electroporation for localised prostate cancer
Authors: Scheltema Matthijs J. , Geboers Bart , Blazevski Alexandar , Doan Paul , Katelaris Athos , Agrawal Shikha , Barreto Daniela , Shnier Ron , Delprado Warick , Thompson James E. , Stricker Phillip D.
Published: December 2022

Objectives

To evaluate longer‐term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow‐up of 5 years (up to 10 years).

Patients and Methods

All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow‐up were analysed. Follow‐up included 6‐month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate‐specific antigen (PSA) levels. Failure‐free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy.

Results

A total of 229 patients were analysed with a median (interquartile range [IQR]) follow‐up of 60 (40–80) months. The median (IQR) age was 68 (64–74) years, the median (IQR) PSA level was 5.9 (4.1–8.2) ng/mL, and 86% harboured intermediate‐risk disease and 7% high‐risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17–53) months after IRE. Kaplan–Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis‐free survival was 99.6% (228/229), PCa‐specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow‐up biopsy and MRI showed a complete ablation in 82% (186/226). Short‐term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%).

Conclusion

Longer‐term follow‐up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long‐term follow‐up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.
Kinetic analysis of endogenous β2‐adrenoceptor‐mediated cAMP GloSensor™ responses in HEK293 cells
Authors: Cullum Sean A. , Veprintsev Dmitry B. , Hill Stephen J.
Published: December 2022

Background and Aim

Standard pharmacological analysis of agonist activity utilises measurements of receptor‐mediated responses at a set time‐point, or at the peak response level, to characterise ligands. However, the occurrence of non‐equilibrium conditions may dramatically impact the properties of the response being measured. Here we have analysed the initial kinetic phases of cAMP responses to β2‐adrenoceptor agonists in HEK293 cells expressing the endogenous β2‐adrenoceptor at extremely low levels.

Experimental Approach

The kinetics of β2‐adrenoceptor agonist‐stimulated cAMP responses were monitored in real‐time, in the presence and absence of antagonists, in HEK293 cells expressing the cAMP GloSensor™ biosensor. Potency (EC50) and efficacy (Emax) values were determined at the peak of the agonist GloSensor™ response and compared to kinetic parameters L50 and IRmax values derived from initial response rates.

Key Results

The partial agonists salbutamol and salmeterol displayed reduced relative IRmax values (with respect to isoprenaline) when compared with their Emax values. Except for the fast dissociating bisoprolol, preincubation with β2‐adrenoceptor antagonists produced a large reduction in the isoprenaline peak response due to a state of hemi‐equilibrium in this low receptor reserve system. This effect was exacerbated when IRmax parameters were measured. Furthermore, bisoprolol produced a large reduction in isoprenaline IRmax consistent with its short residence time.

Conclusions and Implications

Kinetic analysis of real‐time signalling data can provide valuable insights into the hemi‐equilibria that can occur in low receptor reserve systems with agonist–antagonist interactions, due to incomplete dissociation of antagonist whilst the peak agonist response is developing.
Schools engaged in doom‐monitoring students' online interactions and content creation: an analysis of dominant media discourses
Authors: Kikerpill Kristjan , Siibak Andra
Published: December 2022

Background

Growing public concern about the safety and security of schools has led many schools and school districts within the United States to hire private companies to monitor students' online interactions and the content they create, including on social media. The use of such technologies supposedly increases schools' awareness of what students are doing online and, thus, helps to identify and prevent potential issues such as mental health problems, cyberbullying, or self‐harm that might otherwise go unnoticed. However, there is currently no evidence to support that social media surveillance or content monitoring is able to effectively address these public health and safety issues.

Methods

Thus, our study explores how the different voices present in the discourse – students, school officials, privacy advocates, and service providers' representatives – justify or condemn the surveillance of student‐produced online content in publicly available news media articles. We adopt a critical discursive psychology approach to study news articles, which were published in international media in the last 3 years (2019 N = 53; 2020 N = 56; 2021 N = 77), reporting on the use of digital surveillance technologies targeting student‐produced content.

Results and conclusions

Three dominant interpretive repertoires emerged from the analyzed news media articles: ‘silenced students, expert adults’, ‘a solution in search of a problem’, and ‘the normalization of surveillance for a good cause’. Our findings show that, under the auspices of protecting children, schools are actively engaged in ‘doom‐monitoring’, which is the indiscriminate and inaccurate surveillance of people in anticipation of the next bad thing. The opinions and views of adults, including school officials, vendors, and civil liberties advocates, dominate over the voices of students.
Aetiology of occupational hand eczema in hairdressers: Tackling the complexity of exposure combinations to identify patterns associated with increased risk of hand eczema
Authors: Havmose Martin S. , Uter Wolfgang , Gefeller Olaf , Johansen Jeanne D.
Published: December 2022

Introduction

Hairdressers are exposed to wet work and manifold allergens at work, rendering exposure complex and the aetiology of occupational hand eczema (OHE) often multifactorial in this occupational group.

Objectives

To identify exposure patterns associated with increased risk of hand eczema in hairdressers.

Methods

All hairdressers graduating from 2004 to 2007 and 2015 to 2018 received a questionnaire in 2009 and 2020, respectively. Current exposures (with or without regular glove use) and OHE were self‐reported, and their association examined. Patterns of exposure were identified by latent class analysis (LCA).

Results

A total response of 39.9% (668/1675) was obtained. Six exposure profiles (#1–6) were identified by LCA across 11 tasks performed with or without gloves as well as deep conditioning, that is, 23 task items. Compared to profile #1 with the lowest OHE risk (reference) an increased risk of current OHE were seen in profile #4 [adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.5–44.8 and #6 (aOR 39.4, 95%CI 6.1–362.8)] in logistic regression analysis. Profile #1 and #6 had performed the same tasks, but in profile #6 regular glove use was performed in 9.1% (1/ 11) of tasks compared to 72.7% (8/11) of tasks in profile #1 (p = 0.002).

Conclusion

Although occupational exposures in hairdressing are complex, meaningful patterns associated with a wide range of OHE risk can be identified by LCA. The increase of OHE risk seems predominantly to be due to poor compliance with protective gloves. LCA could be applied to further fields of complex (skin) exposures.
Impact of faecal haemoglobin based triage of bowel symptoms presenting to primary care on colorectal cancer diagnosis
Authors: Delson Dwi , Ward Mark , Haddock Rosemary , Nobes Jennifer , Digby Jayne , Strachan Judith A. , Mowat Craig
Published: December 2022

Aim

Faecal immunochemical testing (FIT) for faecal haemoglobin was introduced into primary care in National Health Service Tayside in 2015 as an adjunct to clinical assessment of new bowel symptoms. We aimed to assess the impact of FIT‐based triage in primary care on colorectal cancer (CRC) diagnosis.

Method

Cancer audit data between January 2016 and December 2019 were reviewed to identify all patients diagnosed locally with CRC. The mode of presentation and stage at diagnosis were noted and patient records were interrogated to identify whether FIT and full blood count (FBC) had been performed prior to referral. Results were compared between the FIT and non‐FIT groups.

Results

In all, 1245 patients were diagnosed with CRC of whom 581 (46.7%) presented through primary care. FIT was performed prior to referral in 440/581 (75.7%), with the proportion increasing from 62.3% in 2016 to 85.8% in 2019. At faecal haemoglobin ≥10 μg Hb/g faeces, sensitivity for CRC was 94.1%. Over the study period the annual proportion of non‐emergency presentations increased significantly; presentations from primary care increased from 43.1% to 53.5% (P = 0.0096). After excluding non‐FIT patients who had an overt CRC at referral, there was no difference in stage at diagnosis between FIT and non‐FIT cancers. Safety‐netting with FBC was widely used in our cohort with 97.3% of FIT patients having also had FBC.

Conclusion

FIT‐based triage of new bowel symptoms in primary care is associated with increased non‐emergency presentation of CRC but this did not influence stage at diagnosis.
The randomized, single‐ and multiple‐ ascending dose studies of the safety, tolerability, pharmacokinetics of CSPCHA115 in healthy Chinese subjects
Authors: Jing Shan , Liu Wenfang , Yang Kexu , Lin Yang , Yao Xuekun , Sun Guilan
Published: December 2022

CSPCHA115 is a highly selective and potent antagonist of chemoattractant receptor‐homologous molecule expressed on TH2 cells (CRTH2). This study aimed to evaluate the pharmacokinetics (PKs), safety, and tolerability of single and multiple ascending doses of CSPCHA115 in Chinese healthy subjects. Two phase I studies both adopted a randomized, double‐blind, placebo‐controlled, single‐center, and ascending‐dose design. In the single ascending dose (SAD) study, subjects were randomly allocated to receive a single dose of CSPCHA115 (25–1000 mg) or a placebo. In the multiple ascending dose (MAD) study, 100, 200, 400, or 600 mg of CSPCHA115 or placebo were given to subjects once daily for 7 days. PK parameters were estimated by noncompartmental analysis. Safety was assessed by monitoring treatment‐emergent adverse events (TEAEs), clinical laboratory tests, electrocardiograms, vital signs, and physical examinations throughout the study period. Forty‐eight healthy subjects were enrolled in the SAD study, and 40 healthy subjects were in the MAD study. Following single and multiple administrations, CSPCHA115 was rapidly absorbed with a median time to maximum concentration of ~0.5–3.5 h; and the systemic exposure of CSPCHA115 generally increased dose‐proportionally within the dose range studied. Steady‐state was approximately achieved by day 5, and <1.5‐fold accumulation was observed following multiple doses. Mean terminal half‐life was ~8.16–16.43 h after a single dose. CSPCHA115 was well‐tolerated in both studies, with a low overall incidence of TEAEs. The most common TEAE related to CSPCHA115 was hypertriglyceridemia. No significant safety concerns were identified in healthy subjects.
Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects
Authors: Asker Mohammed , Krieger Jean‐Philippe , Liles Amber , Tinsley Ian C. , Borner Tito , Maric Ivana , Doebley Sarah , Furst C. Daniel , Börchers Stina , Longo Francesco , Bhat Yashaswini R. , De Jonghe Bart C. , Hayes Matthew R. , Doyle Robert P. , Skibicka Karolina P.
Published: December 2022

Objectives

Oxytocin (OT) has a well‐established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT‐R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT‐R activation is sufficient to alter energy intake and expenditure.

Methods and Results

We first show that systemic OT potently reduced food intake and food‐motivated behaviour for a high‐fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood‐brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled‐OT (fAF546‐OT, Roxy), for the presence of IP‐injected Roxy in CNS tissue relevant to feeding control and compared such with BBB‐impermeable fluorescent OT‐B12 (fCy5‐OT‐B12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT‐R, we generated a novel BBB‐impermeable OT (OT‐B12), with equipotent binding at OT‐R in vitro. In vivo, IP‐injected OT and OT‐B12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT‐R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT‐B12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose‐dependent reduction of emesis in male shrews. While both OT and OT‐B12 proved to have similar effects on body temperature, only OT resulted in home‐cage locomotor depression.

Conclusions

Together our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT‐R may be a viable strategy to achieve appetite suppression with better patient outcomes.
Non‐target noctuids from traps with synthetic Spodoptera frugiperda pheromone lure in the Carpathian Basin, Central Europe
Authors: Szanyi Szabolcs , Nagy Antal , Varga Zoltán , Tóth Miklós
Published: December 2022

The fall armyworm, Spodoptera frugiperda JE Smith (Lepidoptera: Noctuidae), is one of the most important invasive noctuid pests. Its appearance and rapid spread can be monitored with sex pheromone traps, but the catches can be confused by catches of non‐target similar species. Here we present non‐target catches of commercial pheromone traps of S. frugiperda in the Carpathian basin, which is a potential area of the pest. Sizable catches of Cucullia umbratica (L.), Agrotis bigramma (Esper), and Allophyes oxyacanthae (L.), common noctuids in East‐Central Europe, were recorded in numerous sampling sites. Although they can be distinguished from the target species by their different morphology, it is necessary to draw the attention of agricultural experts to their possible presence in the traps to avoid misleading conclusions.
Dynamic distribution modelling of the swamp tigertail dragonflySynthemis eustalacta(Odonata: Anisoptera: Synthemistidae) over a 20‐year bushfire regime
Authors: Goodman Aaron M. , Kass Jamie M. , Ware Jessica
Published: December 2022

Intensity and severity of bushfires in Australia have increased over the past few decades due to climate change, threatening habitat loss for numerous species. Although the impact of bushfires on vertebrates is well‐documented, the corresponding effects on insect taxa are rarely examined, although they are responsible for key ecosystem functions and services. Understanding the effects of bushfire seasons on insect distributions could elucidate long‐term impacts and patterns of ecosystem recovery.

Here, the authors investigated the effects of recent bushfires, land‐cover change, and climatic variables on the distribution of a common and endemic dragonfly, the swamp tigertail (Synthemis eustalacta) (Burmeister, 1839), which inhabits forests that have recently undergone severe burning. The authors used a temporally dynamic species distribution modelling approach that incorporated 20 years of community‐science data on dragonfly occurrence and predictors based on fire, land cover, and climate to make yearly predictions of suitability. The authors also compared this to an approach that combines multiple temporally static models that use annual data.

The authors found that for both approaches, fire‐specific variables had negligible importance for the models, while the percentage of tree and non‐vegetative cover were most important. The authors also found that the dynamic model outperformed the static ones, based on cross‐validation omission rate. Model predictions indicated temporal variation in area and spatial arrangement of suitable habitat, but no patterns of habitat expansion, contraction, or shifting.

These results highlight not only the efficacy of dynamic modelling to capture spatiotemporal variables such as vegetation cover for an endemic insect species, but also provide a novel approach to mapping species distributions with sparse locality records.
Discordant pattern between realised and fundamental saline niches in two supralittoral Ochthebius species (Coleoptera: Hydraenidae)
Authors: Mirón‐Gatón Juana María , Botella‐Cruz María , García‐Meseguer Antonio José , Millán Andrés , Velasco Josefa
Published: December 2022

Determining the saline niche of the congeneric and co‐existing species that inhabit supralittoral rockpools subjected to extremely fluctuating saline conditions is a crucial concern to understand their spatial distributions and occurrence, and to predict their ability to face increasing environmental instability due to climate change.

Therefore, we compared the realised and fundamental saline niches of Ochthebius quadricollis and Ochthebius lejolisii (Coleoptera: Hydraenidae) on the Mediterranean coast of the Iberian Peninsula.

A realised niche was determined using field data on the abundance of the adults and larvae of both species.

A fundamental niche was addressed with laboratory experiments by measuring the survival of the adults and larvae and the egg‐hatching success exposed to different salinity treatments (35, 60, 90, 110, 140 and 170 g L−1).

Our study found a discordant pattern between realised and fundamental niches. Both species are euryhalines and support extreme salinity fluctuations from 1.80 to almost 140 g L−1, and O. quadricollis larvae in the field withstand up to 180 g L−1.

However, physiological tolerance was greater in O. lejolisii than in O. quadricollis, and O. lejolissi adults survived in the laboratory at 170 g L−1 for more than 3 days with 30% egg‐hatching success, whereas O. quadricollis showed a maximum survival time of 2 days and no egg‐hatching success at that salinity.

The larvae and eggs of both species were more tolerant than adults.

The two studied species exhibited high physiological capacity to tolerate extremely fluctuating salinity, which will be exacerbated by climate change.
Soil texture and pH affect soil CO2 efflux in hardwood floodplain forests of the lower middle Elbe River
Authors: Heger Adrian , Becker Joscha N. , Vásconez Lizeth K. , Holl David , Eschenbach Annette
Published: December 2022

Floodplain ecosystems play a significant role in the global carbon (C) cycle, particularly due to their C sink potential in hardwood floodplain forests. However, in these forests, interactions between a heterogeneous micro‐relief and anthropogenic landscape changes make estimating C loss through soil CO2 efflux difficult. To determine the drivers of soil CO2 efflux, we selected six hardwood floodplain forests at the lower middle Elbe River, which were distributed among different relief positions (low‐lying or high‐elevated) in the active and former flooding zone. We measured soil CO2 effluxes over a full year using the closed‐chamber method. Based on the response of soil CO2 efflux to soil moisture and temperature, annual efflux rates were determined, which were then related to soil properties, such as pH, texture, soil organic carbon (SOC) and nitrogen (N) content. Soil CO2 efflux ranged between 1006 (±99) and 2214 (±118) gC m−2 year−1. Maximum efflux occurred in a former floodplain forest that was disconnected from Elbe River water table fluctuations. SOC‐specific soil CO2 efflux (gC gSOC−1 year−1) was smallest in low‐lying forests of the active flooding zone and reflected by the appearance of redoximorphic mottling close to the soil surface. Fine texture (<6.3 μm), SOC and N were related positively and electric conductivity, C/N and pH negatively to total soil CO2 efflux. Soil pH and fine texture were the strongest univariate predictors for total soil CO2 efflux (both R2 = 0.59). Fine texture, pH and C/N ratio explained 66% of the variance in total soil CO2 efflux according to multiple linear regression. We conclude that, in hardwood floodplain forests, soil CO2 efflux is mainly controlled by fine texture and soil pH. Fine texture can be related to soil moisture and nutrient availability and may have a positive effect on the activity of microorganisms.

Highlights

Soil CO2 efflux ranged between 1006 (±99) and 2214 (±118) gC m2 year−1, whereby the maximum was measured in a disconnected floodplain forest

Maximum soil CO2 efflux was measured in a disconnected floodplain forest

SOC‐specific soil CO2 efflux was smallest in forests where redoximorphic mottling occurred close to the surface

Fine texture (<6.3 μm) and pH were the strongest predictors for annual soil CO2 efflux
Using model simulation to evaluate soil loss potential in diversified agricultural landscapes
Authors: Koch Tobias , Deumlich Detlef , Chifflard Peter , Panten Kerstin , Grahmann Kathrin
Published: December 2022

Agricultural production is facing a challenging transition through changing political framework conditions and climate change. Innovative field use and land management through temporal and spatial diversification measures support the political efforts to achieve the European Green Deal. However, increasing precipitation intensities through climate change are leading to an increased risk of soil erosion by water. To mitigate such risk, soil erosion should be taken into account when redesigning fields and landscapes. This paper aims to assess the present erosion risk situation in the innovative on‐farm field experiment “patchCROP” with several implemented spatio‐temporal crop diversification measures (field size, flower strips, crop rotation), using the physically‐based Erosion 3D simulation model at the field scale. The modelling results showed that field reshaping from one large field into smaller field segments had the potential to reduce soil erosion. Flower strips reduced the sediment discharge to approximately half of that of small field segments without flower strips. However, as model results indicated, heterogeneous landscapes showed complex erosion and deposition patterns. To identify these, making use of physically based soil erosion models in new field arrangements is a critical future task.

Highlights

Evaluation of a physically based soil erosion model that can be integrated into field re‐design.

Patch crop systems promise to enable higher spatial field diversification.

Equal consideration of minor site‐specific topography and modified field design needed to prevent soil erosion.

Physically based soil erosion models offer a powerful tool to optimise design of future cropping systems.
Manganese reduction regulates soil organic carbon loss from an acidified Cambisol
Authors: Zhou Shiwei , Kong Jiaming , Song Zhizhong , Zhang Xiaolong , Bi Xiaoli
Published: December 2022

Soil acidification has occurred and accelerated in Jiaodong Peninsula, China, causing serious problems, such as manganese (Mn) toxicity and soil organic carbon (SOC) losses. However, the relationships between SOC and soil Mn are still unclear. This study aimed to explore the changes of Mn fractions and SOC under soaking conditions and the acidification‐induced positive coupled relationship between them. A sequential extraction for Mn species after acid soaking of a Cambisol was conducted, and the soil (pre‐ and post‐soaking) was characterised by X‐ray diffraction (XRD) and scanning electron microscope (SEM). The results showed that acidification of a Cambisol (from pH 6.48 to pH 2.79) induced SOC losses (15.8% of initial SOC). Meanwhile, lower mobile or immobile Mn (especially oxide‐Mn) significantly decreased, accompanied by an increase in readily soluble Mn. It was further shown that the amount of decrease in free Mn reached 268.7 mg kg−1, accounting for 93.8% of the total loss of soil Mn, indicating that the reductive dissolution of amorphous Mn (III/IV) oxides is the dominant reaction in acidified Cambisols. This result was also supported by XRD and SEM. Correlation analysis showed that under soil acidification, the reductive dissolution of amorphous Mn (III/IV) oxides drove losses of both SOC and soil Mn. Therefore, a possible reaction mechanism was proposed: at neutral and alkaline pH, immobile complexes of Mn (III/IV) and particulate organic carbon (POC) formed; and, at acidic pH, readily mobile complexes of Mn (II) and dissolved organic carbon (DOC) formed. Our research suggested that Mn‐organic carbon complexes regulated the transport, transformation, and leaching of soil Mn and SOC, and future research should focus on the soil acidification‐driven Mn reduction‐carbon oxidation processes.

Highlights

Acidification accelerated soil organic carbon losses.

Acidification induced reductive dissolution of amorphous Mn (III/IV) oxides.

A positive couple relationship between SOC and soil Mn existed in acidified soils.
Maternal cannibalistic preferences affect offspring preferences and development in Menochilus sexmaculatus Fabricius (Coleoptera: Coccinellidae): A transgenerational investigation
Authors: Yadav Tripti , Omkar  , Mishra Geetanjali
Published: December 2022

Cannibalism has been widely reported across taxa. However, the heritability and expression of cannibalistic traits have been least explored. The variation in the expression of cannibalism is likely to exist amongst the population affecting the propensity of cannibalism. Thus, to know whether the mother has any role in the transgenerational transmission of this trait in a ladybird beetle, Menochilus sexmaculatus, we studied the interaction between maternal and offspring prey preferences and its effect on, development duration and body weight of offspring over generations. An insignificant effect of maternal dietary history on offspring prey preference was observed across generations except for the non‐cannibalistic adults who significantly preferred aphids over eggs. The long‐term detrimental effect of cannibalism was found in cannibals with increased developmental duration and decreased body weight of offspring over generations. In conclusion, the results show that maternal diet did not affect the offspring preferences in M. sexmaculatus but cannibalism had a profound generational effect on the cannibalistic propensity, development and body weight of offspring across generations shows that larval dietary history and nutritional composition of prey contribute to the expression of cannibalistic behaviour across generations.
Early‐warning signal recognition methods in flawed sandstone subjected to uniaxial compression
Authors: Lei Ruide , Berto Filippo , Hu Chao , Lu Zhaohui , Yan Xufeng
Published: December 2022

To investigate the precursor information related to rock fracturing, a series of indoor uniaxial compression tests are conducted on flawed sandstone. Four methods of identifying potential precursors to rock catastrophic failure, namely, cumulative acoustic emission (AE) activity, AE b‐value, inter‐event time function, and critical slowing down, are discussed. The results show that the four precursory identification methods can reasonably identify the early‐warning signal, subcritical failure, and final catastrophic failure of flawed sandstone involving the whole loading process. The minimum b‐value is correspondingly obtained when the specimen approaches failure. The inter‐event rate of AE multi‐parameters shows a significant increase, following a power law distribution. By comparison with the other three precursor identification methods, the time intervals of AE parameters‐based variance between the precursory signal and its corresponding tripping points become increasingly shortened. Additionally, the precursory characteristics of variance of AE multi‐parameters are more accurate and reliable than that of autocorrelation coefficient.
Microstructural characteristics and its correlation to mechanical properties of additively manufactured nickel‐base superalloy upon heat treatments
Authors: Pei Changhao , Yuan Huang
Published: December 2022

The IN718 superalloy was additively manufactured in three different heat treatment states and three loading directions (0°, 45°, 90°). The anisotropic mechanical properties were investigated based on microstructural analysis and related to the orientation and heat treatments. The differences in mechanical performances are attributed to the precipitation hardening and the impediment of dislocation motion from
particles. The preferential epitaxial grain growth along the building direction and the resulting
texture are considered responsible for the anisotropic tensile strength. The Weibull distribution and the area‐weighted grain diameter were presented to characterize the grain distributions. The Hall–Petch relation was established to correlate the directional grain size and the yield strength of AM IN718, which further illustrated the dominance of precipitates in strengthening mechanisms and the effects of subgrain boundaries.
Revisiting the role of early life growth for survival potential in three clupeoid species
Authors: Tanaka Shota , Togoshi Shizuna , Yasue Naotaka , Burns Corinne M. , Robert Dominique , Takasuka Akinori
Published: December 2022

Johan Hjort's “critical period” hypothesis, which postulates that year‐class strength is determined in the short period following the onset of exogenous feeding, has rarely been supported by empirical data. Instead, the current understanding is that recruitment is determined by cumulative mortality throughout early life. Recent studies relied on the measure of growth autocorrelation derived from otolith daily increment widths to test the link between growth rate achieved during the post‐hatch period and during subsequent phases of the larval stage. Based on this approach, we revisit the role of larval growth in driving survival potential in three clupeoid species: Japanese sardine Sardinops melanostictus, Japanese anchovy Engraulis japonicus, and Pacific round herring Etrumeus micropus throughout the larval stage, using a combination of published datasets of otolith increment widths. Strong growth autocorrelation was detected for all three species throughout the larval stage, suggesting that initial growth determines to some extent growth rates achieved later in life. The extent of autocorrelation was reduced in sardine relative to anchovy and round herring at older ages. This interspecific difference could be attributed to differences in sensitivity to variability of environmental factors such as water temperature and food availability. The present findings suggest that the effect of early growth rate persists into later life stages for driving survival potential, which could reconcile the classic concept of “critical period” and the current “growth–survival” paradigm.