bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgens and estrogens predict sexual function after autologous hematopoietic stem cell transplant in men
Authors: Anderson Lindsey J. , Migula Dorota , Abay Rebecca , Crabtree Stephanie , Graf Solomon A. , Matsumoto Alvin M. , Chauncey Thomas R. , Garcia Jose M.
Published: October 2021

Background

Autologous hematopoietic stem cell transplantation (AHSCT) is associated with sexual dysfunction and hypogonadism. Androgens are associated with sexual function in healthy men, but the role of estrogens is less well‐known, and the association of these sex steroids with sexual function during AHSCT has not been characterized.

Objectives

The purpose of this study was to determine the predictive value of sex hormones before and acutely after AHSCT on sexual function recovery.

Materials and methods

We examined sex hormones and self‐reported sexual function before (PRE) and 1‐month post‐AHSCT (MONTH1; n = 19), and sexual function again 1‐year post‐AHSCT in men (YEAR1; n = 15).

Results

Sexual function decreased from PRE to MONTH1 (p ≤ 0.05) with no differences between PRE and YEAR1. Erectile dysfunction was prevalent at PRE (68.4%) and increased at MONTH1 (100%; p ≤ 0.05) but was not different between PRE and YEAR1 (60.0%). From PRE to MONTH1, total testosterone (TT), dihydrotestosterone (DHT), follicle‐stimulating hormone, and sex‐hormone‐binding globulin (SHBG) increased (p ≤ 0.02) while estradiol (p ≤ 0.026) and estrone decreased (p ≤ 0.001). MONTH1 TT and DHT were associated with sexual function at MONTH1, while PRE SHBG, MONTH1 estradiol, and change in estrone predicted sexual function at YEAR1.

Discussion

Sexual dysfunction is very prevalent prior to AHSCT and is transiently and severely worsened acutely after. AHSCT induces acute decreases in total and free estrogens, with SHBG increases leading to increases in total androgens, without changes in free androgens.

Conclusion

Androgens and estrogens are both adversely affected by AHSCT but may predict sexual dysfunction in this population. This supports the premise that estrogen impacts sexual function independent from androgens and that steroid hormones are associated with acute changes in sexual function in this setting. Larger, controlled trials with long‐term sex hormone assessment will need to confirm the association between early changes in estrogens and long‐term sexual function recovery.
Patterns of care and outcomes for gastric and gastro‐oesophageal junction cancer in an Australian population
Authors: Abbas M Nazim , Bright Tim , Price Timothy , Karapetis Christos , Thompson Sarah , Connell Caroline , Watson David , Barnes Mary , Bull Jeff , Singhal Nimit , Roy Amitesh
Published: October 2021

Background

A single state‐wide upper gastrointestinal (GI) cancer video‐linked multidisciplinary team (MDT) meeting guides management and evidence‐based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro‐oesophageal junction (GOJ) cancers.

Methods

Patients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage‐specific survival outcomes were determined and analysed for each treatment modality.

Results

The study included 218 patients and at diagnosis 132 (61%) patients had stage I–III and 86 (39%) patients had stage IV disease. One hundred and ninety‐five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty‐six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6‐NR), 22.8 (95% CI 20.4–43.2), and 6.0 months (95% CI 4.8–8.4) respectively (p < 0.001). Median overall survival for patients who underwent perioperative chemotherapy and surgery was not reached as compared to 44.4 months (95% CI 28.8‐NR) for patients who underwent surgery alone.

Conclusion

Treatment outcomes for patients with gastric and GOJ cancer managed across South Australia met contemporary evidence‐based practice. However, as most patients continue to present with late‐stage disease, longer‐term survival remains poor.
Prediction model for hepatocellular carcinoma occurrence in patients with hepatitis C in the era of direct‐acting anti‐virals
Authors: Tahata Yuki , Sakamori Ryotaro , Yamada Ryoko , Kodama Takahiro , Hikita Hayato , Hagiwara Hideki , Imai Yasuharu , Hiramatsu Naoki , Tamura Shinji , Yamamoto Keiji , Oshita Masahide , Ohkawa Kazuyoshi , Hijioka Taizo , Fukui Hiroyuki , Ito Toshifumi , Doi Yoshinori , Yamada Yukinori , Yakushijin Takayuki , Yoshida Yuichi , Tatsumi Tomohide , Takehara Tetsuo ,   the Osaka Liver Forum
Published: October 2021

Background

Several factors associated with hepatocellular carcinoma (HCC) occurrence after sustained virological response (SVR) in patients with hepatitis C have been reported. However, few validation studies have been performed in the era of direct‐acting anti‐virals (DAAs).

Aims

To develop a prediction model for HCC occurrence after DAA‐mediated SVR and validate its usefulness.

Methods

We analysed 2209 patients with SVR and without a history of HCC who initiated DAA treatment at 24 Japanese hospitals. These patients were divided into a training set (1473 patients) and a validation set (736 patients).

Results

In the training set, multivariate Cox proportional hazards analysis showed that the baseline BMI (≥25.0 kg/m2, P = 0.024), baseline fibrosis‐4 (FIB‐4) index (≥3.25, P = 0.001), albumin level at SVR (<4.0 g/dL, P = 0.010) and alpha‐foetoprotein level at SVR (≥5.0 ng/mL, P = 0.006) were significantly associated with HCC occurrence. We constructed a prediction model for HCC occurrence with these four factors (2 points were added for the FIB‐4 index, and 1 point was added for each of the other three factors). Receiver operating characteristics curve analysis identified a score of 2 as the optimal cut‐off value for the prediction model (divided into 0‐1 and 2‐5). In the validation set, the sensitivity and negative predictive value for HCC occurrence were 87.5% and 99.7%, respectively, at 2 years and 71.4% and 98.0%, respectively, at 3 years.

Conclusion

A prediction model combining these four factors contributes to an efficient surveillance strategy for HCC occurrence after DAA‐mediated SVR.
Usefulness of structured‐cadaveric training for trans‐anal pelvic exenteration
Authors: Tominaga Tetsuro , Nonaka Takashi , Fukuda Akiko , Moriyama Masaaki , Oyama Shosaburo , Ishii Mitsutoshi , Takamura Keiko , Tsurumoto Toshiyuki , Sawai Terumitsu , Nagayasu Takeshi
Published: October 2021

Purpose

Structured training using cadaveric simulation is useful for trans‐anal surgery; however, no studies have examined the effectiveness of cadaveric training for advanced trans‐anal surgery including pelvic exenteration (PE).

Methods

Twelve colorectal surgeons attended a total of 10 cadaveric simulation training courses between 2016 and 2021 and completed a questionnaire at the end of the program. We divided 14 consecutive patients who underwent trans‐anal PE between 2015 and 2021 into two groups: pre‐training group and post‐training group, and compared the clinico‐pathological features between the groups.

Results

The median length of clinical experience of the surgeons was 12 years. There was high score agreement among the surgeons that the course was useful for recognition of anatomical and layer structure, training for trans‐anal total mesorectal excision and trans‐anal PE, and reducing complications specific to the trans‐anal approach. Compared with the pre‐training group, patients in the post‐training group had a higher rate of two‐team surgery (77.8% vs 0%, P = .021), and shorter time to specimen removal (273 vs 423 min, P = .045).

Conclusions

Structured‐cadaveric training has potential use as a technical step‐up in advanced trans‐anal surgery that might contribute to better short‐term outcomes in the clinical setting.
Business Combinations under Common Control: Filling a Gap in IFRS Standards
Authors: Tarca Ann
Published: October 2021

The aim of this paper is to explain the International Accounting Standards Board's (IASB) preliminary views for accounting for business combinations under common control, an issue not currently addressed in International Financial Reporting Standards. Such combinations are widespread and the accounting for them is diverse. The IASB's preliminary views aim to reduce diversity in practice and to improve the information provided to investors so they can understand the effects of these transactions and compare companies that undertake them.

Accounting for business combinations under common control is not currently addressed in International Financial Reporting Standards. The author describes some of the International Accounting Standard Board's proposals to reduce diversity and improve investors’ information in this area.
Population pharmacokinetics and target attainment analysis of linezolid in multidrug‐resistant tuberculosis patients
Authors: Tietjen Anna K. , Kroemer Niklas , Cattaneo Dario , Baldelli Sara , Wicha Sebastian G.
Published: October 2021

Aim

This study investigates the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of linezolid in patients infected with multidrug‐resistant (MDR) tuberculosis (TB).

Methods

A pharmacometric model was developed including 244 timed linezolid concentration samples from 39 patients employing NONMEM 7.4. The probability of target attainment (PTA, PK/PD target: unbound (f) area‐under‐the‐concentration‐time‐curve (AUC)/minimal inhibitory concentration (MIC) of 119) as well as a region‐specific cumulative fraction of response (CFR) were estimated for different dosing regimens.

Results

A one‐compartment model with linear elimination with a clearance (CL) of 7.69 L/h (interindividual variability 34.1%), a volume of distribution (Vd) of 45.2 L and an absorption constant (KA) of 0.679 h−1 (interoccasion variability 143.7%) allometric scaled by weight best described the PK of linezolid. The PTA at an MIC of 0.5 mg/L was 55% or 97% if patients receiving 300 or 600 mg twice daily, respectively. CFRs varied greatly among populations and geographic regions. A desirable global CFR of ≥90% was achieved if linezolid was administered at a dose of 600 mg twice daily but not at a dose of 300 mg twice daily.

Conclusion

This study showed that a dose of 300 mg twice daily of linezolid might not be sufficient to treat MDR‐TB patients from a PK/PD perspective. Thus, it might be recommendable to start with a higher dose of 600 mg twice daily to ensure PK/PD target attainment. Hereby, therapeutic drug monitoring and MIC determination should be performed to control PK/PD target attainment as linezolid shows high variability in its PK in the TB population.
The immune landscape in BCR‐ABL negative myeloproliferative neoplasms: inflammation, infections and opportunities for immunotherapy
Authors: Strickland Marie , Quek Lynn , Psaila Bethan
Published: October 2021

Breakpoint cluster region‐Abelson (BCR‐ABL) negative myeloproliferative neoplasms (MPNs) are chronic myeloid neoplasms initiated by the acquisition of gene mutation(s) in a haematopoietic stem cell, leading to clonal expansion and over‐production of blood cells and their progenitors. MPNs encompass a spectrum of disorders with overlapping but distinct molecular, laboratory and clinical features. This includes polycythaemia vera, essential thrombocythaemia and myelofibrosis. Dysregulation of the immune system is key to the pathology of MPNs, supporting clonal evolution, mediating symptoms and resulting in varying degrees of immunocompromise. Targeting immune dysfunction is an important treatment strategy. In the present review, we focus on the immune landscape in patients with MPNs – the role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation. Further detailed work is required to delineate immune perturbation more precisely in MPNs to determine how and why vulnerability to infection differs between clinical subtypes and to better understand how inflammation results in a competitive advantage for the MPN clone. These studies may help shed light on new designs for disease‐modifying therapies.
Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins
Authors: Abdeen Suhair , Abu‐Fanne Rami , Bdeir Khalil , Maraga Emad , Higazi Mohamed , Cines Douglas B. , Heyman Samuel N. , Higazi Abd Al‐Roof
Published: October 2021

Patients who are severely affected by coronavirus disease 2019 (COVID‐19) may develop a delayed onset ‘cytokine storm’, which includes an increase in interleukin‐6 (IL‐6). This may be followed by a pro‐thrombotic state and increased D‐dimers. It was anticipated that tocilizumab (TCZ), an anti‐IL‐6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID‐19. However, clinical trials with TCZ have recorded an increase in D‐dimer levels. In contrast to TCZ, colchicine reduced D‐dimer levels in patients with COVID‐19. To understand how the two anti‐inflammatory agents have diverse effects on D‐dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID‐19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL‐6, α‐Defensin (α‐Def), a pro‐thrombotic peptide, and D‐dimers. In contrast, treatment with colchicine reduced α‐Def and Di‐dimer levels. In vitro studies show that IL‐6 stimulated the release of α‐Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL‐6; raising the possibility that the increase in IL‐6 in patients with COVID‐19 treated with TCZ triggers the release of α‐Def, which promotes pro‐thrombotic events reflected in an increase in D‐dimer levels.
Pharmacological characterization of novel heteromeric GluCl subtypes from Caenorhabditis elegans and parasitic nematodes
Authors: Lamassiaude Nicolas , Courtot Elise , Corset Angélique , Charvet Claude L. , Neveu Cédric
Published: October 2021

Background and Purpose

Macrocyclic lactones are the most widely used broad‐spectrum anthelmintic drugs for the treatment of parasitic nematodes affecting both human and animal health. Macrocyclic lactones are agonists of the nematode glutamate‐gated chloride channels (GluCls). However, for many important nematode species, the GluCls subunit composition and pharmacological properties remain largely unknown. To gain new insights into GluCl diversity and mode of action of macrocyclic lactones, we identified and pharmacologically characterized receptors made of highly conserved GluCl subunits from the model nematode Caenorhabditis elegans, the human filarial nematode Brugia malayi and the horse parasite Parascaris univalens.

Experimental Approach

AVR‐14, GLC‐2, GLC3 and GLC‐4 are the most conserved GluCl subunits throughout the Nematoda phylum. For each nematode species, we investigated the ability of these subunits to form either homomeric or heteromeric GluCls when expressed in Xenopus laevis oocytes and carried out detailed pharmacological characterization of the functional channels.

Key Results

A total of 14 GluCls were functionally reconstituted, and heteromers formation was inferred from pharmacological criteria. The GLC‐2 subunit plays a pivotal role in the composition of heteromeric GluCls in nematodes. We also found a novel GluCl subtype, combining GLC‐2/GLC‐3 subunits, for which a high concentration of the anthelmintics ivermectin and moxidectin reversibly potentiates glutamate‐induced response.

Conclusion and Implications

This study brings new insights into the diversity of GluCl subtypes in nematodes and promotes novel drug targets for the development of the next generation of anthelmintic compounds.
Treatment with senicapoc, a KCa3.1 channel blocker, alleviates hypoxaemia in a mouse model of acute respiratory distress syndrome
Authors: Petersen Asbjørn Graver , Lind Peter Carøe , Mogensen Susie , Jensen Anne‐Sophie Bonde , Granfeldt Asger , Simonsen Ulf
Published: October 2021

Background and Purpose

Acute respiratory distress syndrome (ARDS) is characterized by pulmonary oedema and severe hypoxaemia. We investigated whether genetic deficit or blockade of calcium‐activated potassium (KCa3.1) channels would counteract pulmonary oedema and hypoxaemia in ventilator‐induced lung injury, an experimental model for ARDS.

Experimental Approach

KCa3.1 channel knockout (Kccn4‐/‐) mice were exposed to ventilator‐induced lung injury. Control mice exposed to ventilator‐induced lung injury were treated with the KCa3.1 channel inhibitor, senicapoc. The outcomes were oxygenation (PaO2/FiO2 ratio), lung compliance, lung wet‐to‐dry weight and protein and cytokines in bronchoalveolar lavage fluid (BALF).

Key Results

Ventilator‐induced lung injury resulted in lung oedema, decreased lung compliance, a severe drop in PaO2/FiO2 ratio, increased protein, neutrophils and tumour necrosis factor‐alpha (TNF‐α) in BALF from wild‐type mice compared with Kccn4‐/‐ mice. Pretreatment with senicapoc (10–70 mg·kg−1) prevented the reduction in PaO2/FiO2 ratio, decrease in lung compliance, increased protein and TNF‐α. Senicapoc (30 mg·kg−1) reduced histopathological lung injury score and neutrophils in BALF. After injurious ventilation, administration of 30 mg·kg−1 senicapoc also improved the PaO2/FiO2 ratio and reduced lung injury score and neutrophils in the BALF compared with vehicle‐treated mice. In human lung epithelial cells, senicapoc decreased TNF‐α‐induced permeability.

Conclusions and Implications

Genetic deficiency of KCa3.1 channels and senicapoc improved the PaO2/FiO2 ratio and decreased the cytokines after a ventilator‐induced lung injury. Moreover, senicapoc directly affects lung epithelial cells and blocks neutrophil infiltration in the injured lung. These findings indicate that blocking KCa3.1 channels is a potential treatment in ARDS‐like disease.
Shoreline evolution from the Late Cretaceous to the Miocene: A record of eustasy, tectonics and palaeoceanography in the Gippsland Basin
Authors: Mahon E. M. , Wallace M. W.
Published: October 2021

Well‐developed clastic shoreline systems have been deposited in the Gippsland Basin over a 70 Ma period, from the latest Cretaceous to the present day. Twenty‐three stacked coastal units have been mapped and described in the Traralgon and Balook formations of the Latrobe and Seaspray groups. These units are made up of prograding and backstepping shoreface deposits, which, in plan view, display well‐developed strandline geometries at the terrestrial–marine interface. Shoreface deposits are interpreted to include prograding beach, barrier island and transgressive beach deposits. The lower coastal plain is characterised by persistent deposition of coals despite changes in shoreface type and significant palaeoclimate fluctuations. These coastal deposits display approximately 123 km of transgression from the Late Cretaceous shoreline at the base of the study interval to the mid Miocene Yallourn Formation near the top. The Late Cretaceous and Palaeocene shoreline deposits individually prograde and are separated by flooding surfaces reflecting eustatic changes. Overall they display long‐term backstepping behaviour (retrogradation) as a result of basin subsidence. Though shorelines of the Eocene–Miocene are distinctly transgressional, probably reflecting basin subsidence, in the mid‐Miocene they become individually and collectively progradational. A series of unconformities in the Oligocene, coupled with Miocene progradation, likely reflects a combination of a compressional tectonic regime and glacioeustatic fluctuations. Despite major changes in the tectonics and palaeoclimate, basin subsidence appears to be the dominant driver for changes in shoreline location.
A pan‐metazoan concept for adult stem cells: the wobbling Penrose landscape
Authors: Rinkevich Baruch , Ballarin Loriano , Martinez Pedro , Somorjai Ildiko , Ben‐Hamo Oshrat , Borisenko Ilya , Berezikov Eugene , Ereskovsky Alexander , Gazave Eve , Khnykin Denis , Manni Lucia , Petukhova Olga , Rosner Amalia , Röttinger Eric , Spagnuolo Antonietta , Sugni Michela , Tiozzo Stefano , Hobmayer Bert
Published: October 2021

Adult stem cells (ASCs) in vertebrates and model invertebrates (e.g. Drosophila melanogaster) are typically long‐lived, lineage‐restricted, clonogenic and quiescent cells with somatic descendants and tissue/organ‐restricted activities. Such ASCs are mostly rare, morphologically undifferentiated, and undergo asymmetric cell division. Characterized by ‘stemness’ gene expression, they can regulate tissue/organ homeostasis, repair and regeneration. By contrast, analysis of other animal phyla shows that ASCs emerge at different life stages, present both differentiated and undifferentiated phenotypes, and may possess amoeboid movement. Usually pluri/totipotent, they may express germ‐cell markers, but often lack germ‐line sequestering, and typically do not reside in discrete niches. ASCs may constitute up to 40% of animal cells, and participate in a range of biological phenomena, from whole‐body regeneration, dormancy, and agametic asexual reproduction, to indeterminate growth. They are considered legitimate units of selection. Conceptualizing this divergence, we present an alternative stemness metaphor to the Waddington landscape: the ‘wobbling Penrose’ landscape. Here, totipotent ASCs adopt ascending/descending courses of an ‘Escherian stairwell’, in a lifelong totipotency pathway. ASCs may also travel along lower stemness echelons to reach fully differentiated states. However, from any starting state, cells can change their stemness status, underscoring their dynamic cellular potencies. Thus, vertebrate ASCs may reflect just one metazoan ASC archetype.
Prediction of the effects of radiation therapy in esophageal cancer using diffusion and perfusion MRI
Authors: Wang Peiliang , Wang Xin , Xu Liang , Yu Jinming , Teng Feifei
Published: October 2021

Chemoradiation therapy (CRT) of locally advanced esophageal cancer (LAEC), although improving outcomes of patients, still results in 50% of local failure. An early prediction could identify patients at high risk of poor response for individualized adaptive treatment. We aimed to investigate physiological changes in LAEC using diffusion and perfusion magnetic resonance imaging (MRI) for early prediction of treatment response. In the study, 115 LAEC patients treated with CRT were enrolled (67 in the discovery cohort and 48 in the validation cohort). MRI scans were performed before radiotherapy (pre‐RT) and at week 3 during RT (mid‐RT). Gross tumor volume (GTV) of primary tumor was delineated on T2‐weighted images. Within the GTV, the hypercellularity volume (VHC) and high blood volume (VHBV) were defined based on the analysis of ADC and fractional plasma volume (Vp) histogram distributions within the tumors in the discovery cohort. The median GTVs were 28 cc ± 2.2 cc at pre‐RT and 16.7 cc ± 1.5 cc at mid‐RT. Respectively, VHC and VHBV decreased from 4.7 cc ± 0.7 cc and 5.7 cc ± 0.7 cc at pre‐RT to 2.8 cc ± 0.4 cc and 3.5 cc ± 0.5 cc at mid‐RT. Smaller VHC at mid‐RT (area under the curve [AUC] = 0.67, P = .05; AUC = 0.66, P = .05) and further decrease in VHC at mid‐RT (AUC = 0.7, P = .01; AUC = 0.69, P = .03) were associated with longer progression‐free survival (PFS) in both discovery and validation cohort. No significant predictive effects were shown in GTV and VHBV at any time point. In conclusion, we demonstrated that VHC represents aggressive subvolumes in LAEC. Further analysis will be carried out to confirm the correlations between the changes in image‐phenotype subvolumes and local failure to determine the radiation‐resistant tumor subvolumes, which may be useful for dose escalation.
Preparation and biological evaluation of new antimicrotubule agents: Modification of the imidazolidin‐2‐one moiety of phenyl 4‐(2‐oxoimidazolidin‐1‐yl)benzenesulfonates
Authors: Gagné‐Boulet Mathieu , Bouzriba Chahrazed , Chavez Alvarez Atziri Corin , Fortin Sébastien
Published: October 2021

We prepared and biologically evaluated 32 novel molecules named phenyl 4‐(dioxoimidazolidin‐1‐yl)benzenesulfonates (PID‐SOs) and ethyl 2‐(3‐(4‐(phenoxysulfonyl)phenyl)ureido)acetates (EPA‐SOs). The antiproliferative activity of PID‐SOs and EPA‐SOs was assessed on four cancer cell lines (HT‐1080, HT‐29, M21, and MCF7). The most potent PID‐SOs bearing an imidazolidin‐2,4‐dione group show antiproliferative activity in the nanomolar to low micromolar range (0.066 – 6 µM) while EPA‐SOs and PID‐SOs bearing an imidazolidin‐2,5‐dione moiety are mostly not active, exhibiting antiproliferative activity over 100 µM. The most potent PID‐SOs (16–18) arrest the cell cycle progression in G2/M phase and interact with the colchicine‐binding site leading to the microtubule and cytoskeleton disruption. Moreover, their antiproliferative activity is not impaired in vinblastine‐, paclitaxel‐, and multidrug‐resistant cell lines. Finally, our study confirms that PID‐SOs bearing the imidazolidin‐2,4‐dione moiety are a new family of promising antimitotics.
Alantolactone: A sesquiterpene lactone with diverse pharmacological effects
Authors: Liu Xin , Bian Lijuan , Duan Xiaoqin , Zhuang Xinming , Sui Yujie , Yang Longfei
Published: October 2021

Alantolactone (Ala) is a sesquiterpene lactone that can be isolated from many herbal plants belonging to Asteraceae. Besides the antimicrobial activities against bacteria, fungi and viruses, Ala has also demonstrated significant anti‐inflammatory effects in various models by inhibiting NF‐κB and MAPKs to decrease the pro‐inflammatory cytokines such as IL‐1β, IL‐6 and TNF‐α. The antitumor effects of Ala have been demonstrated in vitro and in vivo via inducing intrinsic apoptosis, oxidative stress, ER stress, cell cycle arrest and inhibiting autophagy and STAT3 phosphorylation, which are also involved in its combination or synergy with other antitumor drugs. Ala also has neuroprotective activity through attenuating oxidative stress and inflammation, besides its modulation of glucose and lipid metabolism. This review summarizes the recent advances of the pharmacological effects of Ala, including anti‐inflammatory, antitumor, antimicrobial, neuroprotective activities, as well as the underlying mechanisms. Ala might be employed as a potential lead to develop drugs for multiple diseases.
Human (in)security and psychological well‐being in Palestinian children living amidst military violence: A qualitative participatory research using interactive maps
Authors: Veronese Guido , Cavazzoni Federica , Fiorini Alec , Shoman Hala , Sousa Cindy
Published: October 2021

Background

Research has widely evidenced the effects of war and political violence on the functioning of children, with a great accord in diagnosing children's psychological burdens related to their exposure to violence. Yet, within this literature, the influence of the chronic sense of insecurity on their psychological functioning during and after hostilities remains unexplored.

Methods

The present study aimed at exploring interrelated relationships between the perceived insecurity and the children's psychological well‐being and their adjustment to trauma. Based on drawings and walk‐along interviews with 75 Palestinian children, residents of both the West Bank and Gaza Strip, we offer an analysis of human security‐related risks and protective factors that contribute to either promoting or undermining the child's psychological functioning in a context characterized by chronic instability and political violence.

Results

A complex network of sources of security and insecurity emerged from the narratives depicting an ecological portrait encompassing the determinants of children's mental health and psychological functioning. The TCA led to the identification of eight main themes: school and associativism; social relations and house as a source of security/insecurity; military occupation as a source of insecurity; national and political identity as a source of safety; mosque and spirituality as a source of safety/unsafety; environment as a source of security/insecurity; and mental health.

Discussion

An approach encompassing human security as an explicative model can help in exhaustively portraying the complexity of the Palestinian children's suffering and their competence in adjusting to their traumatic reality. The study draws attention to social, political, environmental and economic determinants of children psychological well‐being.
Chronic long‐COVID syndrome: A protracted COVID‐19 illness with neurological dysfunctions
Authors: Baig Abdul Mannan
Published: October 2021

After almost a year of COVID‐19, the chronic long‐COVID syndrome has been recognized as an entity in 2021. The patients with the long‐COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long‐COVID have remained obscure and need to be actively researched to find a resolution for the patients with long‐COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro‐COVID in long‐COVID syndrome.
Surgical closure, mainly with glue injection and anti‐tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial
Authors: Abramowitz Laurent , Brochard Charlène , Pigot François , Roumeguere Pauline , Pillant Hélène , Vinson Bonnet Béatrice , Faucheron Jean Luc , Senéjoux Agnès , Bonnaud Guillaume , Meurette Guillaume , Fayette Jean Marie , Train Cécile , Staumont Ghislain , Siproudhis Laurent , Bouchard Dominique
Published: October 2021

Aim

In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab.

Methods

This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end‐point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula‐related abnormalities.

Results

Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000).

Conclusions

Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.
Examination of Changes in Echo Intensity Following Resistance Exercise among Various Regions of Interest
Authors: Vasenina Ecaterina , Kataoka Ryo , Hammert William B. , Ibrahim Adam H. , Dankel Scott J. , Buckner Samuel L
Published: October 2021

Aim

Within the resistance exercise literature, echo intensity (EI) is often quantified using different regions of interest (ROI).

Purpose

To compare changes in the EI of images of the biceps muscle using different ROI immediately following exercise as well as 24 and 48 h following exercise.

Methods

Twenty seven non‐resistance trained individuals visited the laboratory 4 times. One arm was assigned to the experimental condition, and the other was a non‐exercise control. During visit 1, paperwork and strength were measured. During visit, 2 participant's muscles were imaged before performing biceps curls. Additional muscle images were taken immediately after exercise, as well as 24 and 48 h post. EI was measured using three different ROI: 1) Trace around the entire muscle; 2) Small box placed in the middle of the muscle (2 × 2cm); and 3) Maximal rectangular box. Results are displayed as means (95%CI).

Results

There was no condition (experimental vs. control) x time (pre, post, 24h and 48h) x box size (small, large, full trace) interaction (p = 0·592). However, there was a main effect for box size (p < 0·001). EI values were higher with the small box [28·2 (23·3, 33·1) AU] compared to the large box [26·8 (22·3, 31·2) AU, p = 0·016] and compared to the full trace [24·2 (20·3, 28·0) AU p < 0·001)]. In addition, EI values were higher with the large box compared to the full trace technique (p = 0·001).

Conclusion

Similar changes in EI are detected when using different commonly used ROI for analysing EI. However, when larger ROI are examined, EI values appear to be lower.
Identifying negative sentiment polarity in the Judas technique
Authors: Fitzgerald Austin L. , Josimovich Jillian M. , Robinson Charlotte J. , Reed Robert N. , Currylow Andrea F.
Published: October 2021

In the context of conservation science and management, the Judas technique refers to outfitting an animal (a Judas animal) with a radio transmitter or other identifier so that its movements can be tracked to locate conspecifics. Although this term is commonly used, some consider it offensive due to historical associations of the word Judas with anti‐Semitic sentiments. Thus, the term has a negative sentiment polarity (i.e., the assertion that words can have positive, negative, or neutral connotations). We investigated the etymology of the Judas term in peer‐reviewed scientific literature to outline its contextual introduction and use. Prior to the term being co‐opted by conservation scientists Judas [animal] was a common term in the livestock industry to describe animals used to lead herds to slaughter. Subsequently, the term has been published and promulgated through conservation‐related research and the literature. Due to a negative sentiment polarity linked to this term, especially among members of the public, alternative nomenclature may be preferred to increase objective and dispassionate scientific communication.
Cervical cytology in the detection of uterine clear cell carcinoma: Diagnostic predictors from a case‐control study
Authors: Gupta Parikshaa , Gupta Nalini , Dey Pranab , Bagga Rashmi , Jain Vanita , Suri Vanita
Published: October 2021

Introduction

Uterine clear cell adenocarcinoma (CCC) is a rare, aggressive malignancy with poor prognosis. The present study aimed to identify and describe its characteristic morphological features in cervical cytology.

Methods

This was a 3‐year retrospective case‐control study. Cases included cervical samples of histopathologically proven endometrial and cervical CCC. Controls included cervical samples of histopathologically proven endometrial serous carcinoma (n = 15), endometrioid adenocarcinoma (n = 20), and endocervical adenocarcinoma (n = 15). Twenty‐eight cytomorphological features were evaluated; the strength of association was determined by odds ratio (OR) and Cramer's V, and the diagnostic accuracy of statistically significant features was assessed.

Results

Cases consisted of histopathologically proven 25 (34.7%) endometrial and 13 (18.0%) cervical CCC. Corresponding cervical samples were available for a total of 14 (36.8%) patients, of which 13 (92.8%) were positive for epithelial cell abnormality. On univariate analysis, three cytomorphological variables were significant predictors of uterine CCC: presence of dense cytoplasm (OR = 88; V = 0.72), deep nuclear membrane irregularities (OR = 17.5; V = 0.55), and coarse chromatin (OR = 21.3; V = 0.46). Dense cytoplasm had the highest positive predictive value (92%) and high specificity (97.8%), whereas coarse chromatin had the highest sensitivity (92.3%) and negative predictive value (96.7%).

Conclusions

The presence of dense cytoplasm and deep nuclear membrane irregularities in the tumour cells were strong predictors, and coarse chromatin a moderate predictor, of uterine CCC compared to its close cytological mimics.
Usefulness of contrast‐enhanced endoscopic ultrasonography for the treatment of ethanol reinjection in patient with small pancreatic neuroendocrine neoplasm
Authors: Matsumoto Kazuyuki , Kato Hironari , Okada Hiroyuki
Published: October 2021

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Depoliticising disaster response in a politically saturated context: the case of the 2016–19 droughts in Zimbabwe
Authors: Desportes Isabelle , Moyo‐Nyoni Ntombizakhe
Published: October 2021

Responding to disasters triggered by natural hazards is a deeply political process, but it is usually presented by practitioners as an apolitical endeavour. This is striking when disasters occur in authoritarian and politically highly polarised conflict‐affected settings. Although the literature provides leads as to why and how humanitarians depoliticise aid, there has been little empirical research on the implications of depoliticisation, especially at the community level. Based on qualitative fieldwork that focused on the drought responses that overlapped with the 2016–19 sociopolitical crises in Zimbabwe, this paper details the practices, motivations, and implications of humanitarian depoliticisation. It differentiates between strategic, coerced, and routine managerial depoliticisation, and argues that, in an authoritarian conflict‐affected setting, depoliticisation strategically allows state and non‐state actors to defuse sensitive issues and actor relations and to remain safe. However, depoliticisation can also have implications for information management, monitoring, accountability, and protection, and thus ultimately for upholding humanitarian principles.
Successful follicular unit extraction in a case of inactive, recalcitrant alopecia barbae
Authors: Kerure Amit , Deshmukh Nitika , Bansod Shashank , Sharma Aseem
Published: October 2021

Alopecia areata (AA) is a non‐scarring autoimmune type of alopecia. Hair transplantation in AA is not practiced as the implanted follicular grafts might be destroyed due to underlying autoimmune pathology. A biopsy proven 28 year old male patient of AA presented to us with an 8‐year history of a hairless patch over the beard area. He underwent many treatments by other dermatologist with oral, topical, and intralesional immunosuppressants, which curtailed his disease progression but failed to re‐grow hair. Biopsy during his visit revealed absence of inflammatory infiltrates and empty hair tracts replaced by fibrotic tracts. Follicular unit extraction (FUE) was done successfully after counseling the patient about the controversial role of hair transplant surgery in AA. Hair growth was achieved within 6 months with no recurrence during 1‐year follow up. FUE can be opted for long‐standing and clinically stable cases of AA; histopathology and dermoscopy being the guiding lights in determining the disease inactivity.
Elevated CO2 concentration improves the performance of an agricultural pest: a worrisome climate crisis scenario
Authors: Arantes‐Garcia Lucas , Maia Renata A. , Oki Yumi , Cornelissen Tatiana , Fernandes Geraldo Wilson
Published: October 2021

Carbon dioxide (CO2) emissions are central to the climate crisis and their consequences indiscriminately affect natural and anthropogenic ecosystems. Among ecological interactions, those between plants and insects are among the most impacted by the elevation in CO2 concentration (eCO2). We selected a plant and an herbivore species of worldwide relevance and tested the hypothesis that eCO2 affects leaf quality and defences of sunflower, Helianthus annuus L. (Asteraceae), and negatively impacts the larval preference and performance of the important pest Helicoverpa armigera Hübner (Lepidoptera: Noctuidae). Plants and insects developed inside open‐top chambers under ambient CO2 (ca. 400 ppm) and eCO2 (ca. 800 ppm). Sunflowers under eCO2 grew more (e.g., increased height and had more leaves) but were of lower nutritional quality at an early developmental stage (e.g., lower nitrogen content, greater leaf thickness, and higher flavonoids content). Despite showing no preference for either treatment, H. armigera larvae performed better when fed with leaves from eCO2 plants. We argue this was observed because larvae under eCO2 sustained a greater leaf consumption, even when sunflower leaf quality became similar between treatments (by the 11th week after germination). Besides, they overcompensated a more deficient diet during early developmental stages and presented a higher growth rate; ca. 2.5× more individuals reached the pupal stage, and 4× more individuals became adults. The improvement in H. armigera larval performance under eCO2 indicates a worrisome scenario in which a species that already exerts a significant impact on ecosystems would increase its consumption, develop faster, and support a larger population size.
Dung beetles as hydrological engineers: effects of tunnelling on soil infiltration
Authors: Keller Nadine , van Meerveld Ilja , Ghazoul Jaboury , Chiew Li Yuen , Philipson Christopher D. , Godoong Elia , Slade Eleanor M.
Published: October 2021

1. Soil infiltration capacity determines the partitioning of precipitation into infiltration and overland flow and is therefore an important soil hydrological characteristic. Water infiltration through soil is facilitated by macropores created by roots and soil macrofauna. In clay‐rich soils, such as those of the tropical forests of Sabah, Malaysian Borneo, most infiltration occurs via these preferential flow pathways.

2. We evaluated the effects of dung beetle tunnelling on infiltration and macropore creation (depth and width of the flow pathways) in tropical forest soils in Sabah. Using mesocosms, we applied three treatments (i) soil‐only, (ii) dung‐only, (iii) dung + dung beetles, and measured saturated hydraulic conductivity (i.e., the steady‐state infiltration rate) after 0, 5 and 10 days, and assessed depth and width of infiltration pathways by applying a blue dye tracer.

3. The steady‐state infiltration rate increased in the presence of dung beetles, though differences among treatments were only statistically significant after 10 days. After 5 days of dung beetle presence, infiltrated water had reached a greater depth than the control mesocosms without beetles. However, there were no differences in the width of infiltration pathways among treatments.

4. These results reveal the important, but under studied roles of dung beetles on soil hydrological functioning, that may have consequences for nutrient cycling and plant productivity. Further, our findings indicate that the novel application of an established hydrological method—blue dye tracer—can provide interesting and reliable results for macrofauna–soil interaction studies.
Insecurity, lack of support, and frustration: A sociological analysis of how three groups of students reflect on their distance education during the pandemic in Sweden
Authors: Lidegran Ida , Hultqvist Elisabeth , Bertilsson Emil , Börjesson Mikael
Published: October 2021

This article investigates the situation of Swedish upper secondary school students who have been subject to distance education during the COVID‐19 pandemic crisis. We understand the transition from onsite education to distance education as a recontextualization of pedagogical practice, our framing follows loosely concepts from Bernstein. Given that the field of upper secondary education is highly socially structured it is relevant to enquire into the social dimensions of distance education. For this purpose, we have analysed answers to an open‐ended question in a survey answered by 3,726 students, and related them to a cluster analysis distinguishing three main clusters of students: urban upper‐middle‐class, immigrant working‐class, and rural working‐class. The urban upper‐middle‐class students experienced problems decoding new requirements and were troubled by blurred boundaries between school and home. This group invests the most in schooling, and therefore expresses comparatively more anxiety for reaching anticipated achievements. Immigrant working‐class students were comparatively more discontented by a lack of school support and request clearer instructions. In this new educational situation, characterized by a weak framing, they have difficulties decoding the requirements. The rural working‐class students appear comparatively more disconnected from the school situation. Unlike urban upper‐middle‐class students, for whom the school invades the home and private sphere, the rural working‐class students seldom experienced that the school intruded their home; accordingly, their studies collapsed into sleep‐in‐mornings and a holiday feeling.
Soil phosphorus over a period of agricultural change in Scotland
Authors: Tweedie Andrew , Haygarth Philip M. , Edwards Anthony , Lilly Allan , Baggaley Nikki , Stutter Marc
Published: October 2021

Yield increases by use of phosphorus (P) fertiliser has been a defining aspect of last century's agriculture, but in many countries P inputs are now being regulated to avoid ecological damage and improve agricultural sustainability. We tested the hypothesis that P forms and functions in agricultural soils have changed over a period of 50–70 years of agricultural change using topsoils from 35 agricultural sites in North East Scotland compared at ‘original’ and ‘resampled’ timepoints. The original dried and archived samples were collected between 1951 and 1981, and resampling took place in the autumn of 2017 with all samples reanalysed at the same time and by same methods. A range of soil extractants, from labile (water soluble) P, carbon (C) and nitrogen (N) forms, to surface exchangeable P (acid ammonium oxalate extraction), to complexed P (NaOH‐EDTA extraction), were compared with agronomic soil test P (modified Morgan; MM‐P), soil pH, and, on a subset of five time pairs (n = 10), specific P compounds using 31P NMR spectroscopy. Whilst MM‐P had declined significantly in time, all soils were originally and remained at high soil P status. In contrast, no change in labile P pools, nor in the more refractory P pools that replenish labile P, were observed. In the subset analysed by NMR, orthophosphate P consistently increased in concentration. This suggests that soil P shows a slow (multidecadal) response to the documented reductions in fertiliser P for the study region. Significantly greater soil pH (by 0.4 units) over time and reduced water‐soluble C and N forms suggests that labile P in contemporary soils exists in a biogeochemical environment of enhanced solubility and in excess to other available macronutrients that control its microbial cycling. This study represents a long and important period of changing drivers acting on soil P change with potential to improve understanding future soil P trajectories. The value of archived historical soils samples is shown, if care in interpretation of storage implications is made.

Highlights

Phosphorus fractions in agricultural soil were compared at two timepoints 50–70 years apart.

Whilst soil test P declined with time, other labile and refractory P pools did not change.

The readjustment of P pools is slow even to substantial change in fertiliser inputs.

The investigation of long‐term land use to inform future policy is enabled by soil archives.