bluuebunny/crossref_metadata_2025 huggingface dataset:
Sacubitril/valsartan in real‐life European patients with heart failure and reduced ejection fraction: a systematic review and meta‐analysis
Authors: Giovinazzo Stefano , Carmisciano Luca , Toma Matteo , Benenati Stefano , Tomasoni Daniela , Sormani Maria Pia , Porto Italo , Canepa Marco , Senni Michele , Metra Marco , Ameri Pietro
Published: August 2021

Aims

We systematically reviewed the European real‐world evidence (RWE) about sacubitril‐valsartan for heart failure with reduced ejection fraction.

Methods and results

Twenty‐one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM‐HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random‐effects model meta‐analysis, age was higher (mean difference +3.84, 95% CI 1.92–5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64–0.91), hypertension (OR 0.55, 95% CI 0.37–0.82), and diabetes (OR 0.77, 95% CI 0.64–0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27–5.53) in real‐life than in PARADIGM‐HF. Other clinical and medical features were presented in 19–76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril‐valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23–47) and discontinued in 12.8% (95% CI 7.4–18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all‐cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5–19)/100 person‐year, 8 (95% CI 4–12)/100 person‐year, and 24 (95% CI 5–42)/100 person‐year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects).

Conclusions

Limited‐quality RWE indicates that there are important differences between European patients prescribed sacubitril‐valsartan and the PARADIGM‐HF population, including the frequency of target dose achievement.
Study on thermal performance of casing‐type mine heat recovery device with phase change materials filling in annular space
Authors: Zhang Xiaoyan , Xu Muyan , Liu Lang , Yang Qixing , Song KI‐IL
Published: August 2021

The underground mine contains abundant geothermal energy resources. The casing‐type mine heat recovery device with encapsulated phase change material (PCM) embedded in the backfill body is efficient technology for extraction of geothermal energy in mines. A heat transfer model of a casing‐type mine heat recovery unit was established to study the influence of PCMs thermophysical property and phase transition process on the thermal performance of backfill body. The effects of phase transition temperature, thermal conductivity, specific heat capacity and phase transition latent heat of PCMs on the temperature variation in backfill body and the thermal performance of casing‐type mine heat recovery device were studied in the heat storage/release mode. The result indicates that the phase transition temperature is expected to be lower in heat storage mode and higher in heat release mode, respectively. The heat transfer rate can be significantly enhanced by PCMs with larger thermal conductivity in both heat storage and heat release modes. Furthermore, PCMs with large specific heat capacity and latent heat should be used to improve the energy storage effect. After 10 hours of heat storage/release, when the specific heat capacity increases from 1000 to 3000 J/(kg ∙ K), the heat storage capacity and heat extraction capacity increased by 9.11% and 6.69%, respectively; when the phase transition latent heat increases from 100 to 200 kJ/Kg, the heat storage capacity and heat extraction capacity increased by 4.79% and 3.29%, respectively.
Pollen morphology and its taxonomic significance of the genus Crucianella L. (Rubiaceae) in Iran
Authors: Parsapanah Soheyla , Faghir Marzieh Beygom
Published: August 2021

The Pollen morphology of nine species of Crucianella L. and ten subspecies of C. gilanica representing two sections: Roseae and Crucianella, was investigated using light microscopy (LM) and scanning electron microscopy (SEM). All the studied species (except for C. angustifolia) are palynologically described here for the first time. The results revealed considerable pollen character variation among the studied species. The pollen grains are monads, isopolar, radial symmetrical and relatively small. The largest pollen grains were observed in C. angustifolia (P = 24.12 µm, E = 26.04 µm), while the smallest pollen was found in C. gilanica subsp. carduchorum (P = 16.32 µm, E = 12.57 µm). The outline pollen grains varied from subcircular to circular in polar view and elliptical to quadrangular and circular in equatorial view. The shape of pollen changed from spheroidal to oblate‐spheroidal, prolate‐spheroidal, suboblate, subprolate and prolate. The pollen grains are zonocolpate and their number of colpi ranges from 6 to 10. The results showed five different types of sexine ornamentation: perforate, reticulate, microreticulate, microfoveolate and psilate. The sexine of all examined specimens is covered with microspines. The current survey shows that the pollen morphological characters of the studies species are taxonomically informative and may provide good help in identification purposes. We used multivariate analysis to determine the potential contribution of palynological data to the species relationships. The result of cluster analysis and principal component analysis showed pollen morphological affinities between the two studied sections.
Investigation of the possibility of fermentation of red grape juice and rice flour by Lactobacillusplantarum and Lactobacilluscasei
Authors: Mirmohammadi Royaossadat , Zamindar Nafiseh , Razavi Seyed Hadi , Mirmohammadi Mehrosadat , Paidari Saeed
Published: August 2021

The aim of the current study was to evaluate the possibility of the bacterial growth and substrate metabolism during the fermentation of red grape juice and the mixture of red grape juice and rice flour solution using Lactobacillus plantarum and Lactobacillus casei. In recent years, cereal‐based beverages have been used as functional compounds such as antioxidants, dietary fiber, minerals, probiotics, and vitamins in diets. In this research, fermentation of red grape juice (media 1) and 1:1 mixture of red grape juice and rice flour solution (media 2) by two strains of gram positive and homofermentative lactic acid bacteria: L. plantarum and L. casei (individually and mixed) was examined. Fermentation was carried out at 37°C for 48 hr. Microbial population, pH, acidity, sugar, and organic acid metabolism were measured during the fermentation period. Data showed that in media 2 fermented with mixed culture of both L. plantarum and L. casei, acidity and microbial population increased sharply at the initial stages of fermentation, and the most percentage of lactic acid production occurred. Red grape juice fermented with mixture of L. plantarum and L. casei showed the most sugar consumption (p < .05). Results indicated that the use of the mixture of red grape juice and rice flour solution can be a proper substrate for producing lactic acid.
The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development
Authors: Meir Michael , Maurus Katja , Kuper Jochen , Hankir Mohammed , Wardelmann Eva , Rosenwald Andreas , Germer Christoph‐Thomas , Wiegering Armin
Published: August 2021

Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys‐558‐Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.
Mesozoic–Cenozoic tectonic controls on the formation of large‐scale metamorphic rock buried‐hill reservoirs in Bozhong Sag, eastern China
Authors: Liu Xiaojian , Hou Mingcai , Niu Chengmin , Wang Qingbin , Zhang Xintao , Ye Tao , Cui Puyuan , Hao Yiwei
Published: August 2021

Buried‐hill reservoirs are important targets for petroleum exploration. The number of buried‐hill oil–gas fields with reservoirs hosted in metamorphic rock is low, and metamorphic rock buried‐hill reservoirs deeper than 4,500 m (ultra‐deep) are even rarer. Ultra‐deep metamorphic rock buried‐hill reservoirs are characterized by highly heterogeneous lithologies and structure and have complex formation mechanisms, but such reservoirs have received relatively little research attention compared with reservoirs hosted in other rock types and at shallower depths. In the Bozhong Sag in the Bohai Bay Basin, Archean metamorphic rocks are buried at depths of 4,500–6,000 m, and their anticlinal structures are thus defined as ultra‐deep buried hills. Owing to their burial depth and compacted overburden, tectonism has been a key control on the formation of high‐quality reservoirs by causing deformation such as fractures. In this study, using results of drill‐core analyses, thin‐section imaging, and rock mechanical tests, we investigated the distribution and formation mechanisms of high‐quality reservoirs within the Bozhong 19‐A metamorphic rock buried hill. We also examined the formation mechanism of fractures in the Bozhong 19‐A buried hill with respect to early‐stage initiation by compression and late‐stage reactivation by transpression. Results show that intense compression‐related overthrusting caused by collision between the South China and North China plates during the Indosinian (252–237 Ma) orogeny generated initial fractures in the metamorphic rock buried hill and the formation of numerous NW‐trending nappe structures. Subsequent Yanshanian (163–66 Ma) sinistral transpression not only reactivated pre‐existing fractures, but also resulted in the development of numerous new fractures. In addition, in low‐stress regions such as anticline flanks and the lower parts of structures, compression closed the pre‐existing fractures, leading to lower fracture densities. Results of acoustic emission mechanical testing indicate that Himalayan (66–0 Ma) extensional stress was insufficient to produce large‐scale fracture systems in the Archean metamorphic rock, but was crucial for reactivating pre‐existing early‐stage fractures. Thus, the Himalayan period was a key interval for the formation of effective fractures. Therefore, rocks that underwent large‐scale overthrusting during early‐stage (Indosinian) fracturing and subsequent late‐stage (Yanshanian and Himalayan) reactivation favoured the development of ultra‐deep metamorphic rock buried‐hill reservoirs. This study should provide guidance for petroleum exploration in buried hills in superimposed basins that underwent early‐stage compression, late‐stage transpression, and final extension.
Adenosine A2B receptor down‐regulates metabotropic glutamate receptor 5 in astrocytes during postnatal development
Authors: Tanaka Masayoshi , Shigetomi Eiji , Parajuli Bijay , Nagatomo Hiroaki , Shinozaki Youichi , Hirayama Yuri , Saito Kozo , Kubota Yuto , Danjo Yosuke , Lee Ji Hwan , Kim Sun Kwang , Nabekura Junichi , Koizumi Schuichi
Published: August 2021

Metabotropic glutamate receptor 5 (mGluR5) in astrocytes is a key molecule for controlling synapse remodeling. Although mGluR5 is abundant in neonatal astrocytes, its level is gradually down‐regulated during development and is almost absent in the adult. However, in several pathological conditions, mGluR5 re‐emerges in adult astrocytes and contributes to disease pathogenesis by forming uncontrolled synapses. Thus, controlling mGluR5 expression in astrocyte is critical for several diseases, but the mechanism that regulates mGluR5 expression remains unknown. Here, we show that adenosine triphosphate (ATP)/adenosine‐mediated signals down‐regulate mGluR5 in astrocytes. First, in situ Ca2+ imaging of astrocytes in acute cerebral slices from post‐natal day (P)7‐P28 mice showed that Ca2+ responses evoked by (S)‐3,5‐dihydroxyphenylglycine (DHPG), a mGluR5 agonist, decreased during development, whereas those evoked by ATP or its metabolite, adenosine, increased. Second, ATP and adenosine suppressed expression of the mGluR5 gene, Grm5, in cultured astrocytes. Third, the decrease in the DHPG‐evoked Ca2+ responses was associated with down‐regulation of Grm5. Interestingly, among several adenosine (P1) receptor and ATP (P2) receptor genes, only the adenosine A2B receptor gene, Adora2b, was up‐regulated in the course of development. Indeed, we observed that down‐regulation of Grm5 was suppressed in Adora2b knockout astrocytes at P14 and in situ Ca2+ imaging from Adora2b knockout mice indicated that the A2B receptor inhibits mGluR5 expression in astrocytes. Furthermore, deletion of A2B receptor increased the number of excitatory synapse in developmental stage. Taken together, the A2B receptor is critical for down‐regulation of mGluR5 in astrocytes, which would contribute to terminate excess synaptogenesis during development.
Improvement of patient stratification in human papilloma virus‐associated oropharyngeal squamous cell carcinoma by defining a multivariable risk score
Authors: Oberste Maximilian , Riders Armands , Abbaspour Bektasch , Kerschke Laura , Beule Achim G. , Rudack Claudia
Published: August 2021

Background

Precise risk stratification models are necessary to determine patient selection for deintensifying treatment trials in human papilloma virus (HPV)‐associated oropharyngeal squamous cell cancer (HPV+ OPSCC).

Methods

We examined 526 cases with OPSCC treated at our department between 2002 and 2017. Every patient was classified after the 7th and 8th edition UICC staging manual. For HPV+ OPSCC, we calculated a simple risk score with four risk groups based on multivariable Cox regression analysis of clinical and lifestyle parameters (UICC 8th edition stage, tobacco/alcohol abuse, age, gender).

Results

Two hundred and thirty‐nine patients with OPSCC (45.4%) showed a positive histological HPV status. In comparison to UICC 8th edition stages, our proposed risk model showed a tendency for better stratification between risk strata I/III, I/IV, and II/IV (each p < 0.002) and I/II, II/III, and III/IV (each p < 0.09).

Conclusion

Age, gender, tobacco, and alcohol abuse should be added to the current UICC staging system in order to improve risk stratification in HPV+ OPSCC.
Missed opportunities for improving oral health in rural Victoria: The role of municipal public health planning in improving oral health
Authors: Dickson‐Swift Virginia , Crocombe Leonard
Published: August 2021

Issue addressed

People in rural areas have poorer oral health than their urban counterparts due to a range of factors. Local governments (LGs) have a key role in addressing health issues that impact on local communities.

Methods

Publicly available oral health profile (OHP) data and Municipal Public Health and Wellbeing Plans (MPHWPs) (2017‐2021) were downloaded from Dental Health Services Victoria and LG websites for 48 Victorian local government areas (LGAs) containing predominately rural areas. OHP data were collated to provide an overview of the oral health status of the communities and a content analysis of the MPHWPs undertaken.

Results

Despite poor oral health in rural Victorian LGAs, oral health was not often in MPHWPs. Twenty of the MPHWPs had some mention of oral health but only four included specific actions or strategies that would be used to improve oral health. None of the plans contained any specific targets for action or details of evaluations that might be used to assess success.

Conclusions

Poor oral health in rural Victorian communities continues to be demonstrated through local OHPs and is due to modifiable risk factors and poor access to water fluoridation. LGs have a key role to play in improving oral health through utilisation of OHP data in their MPHWPs.

So what?

Oral health remains a low priority for LG action. This represents a missed opportunity for prioritising oral health prevention and promotion activities that improve oral health in rural Victoria.
Surface electromyography and gamification: Translational research to advance physical rehabilitation
Authors: Vaidya Manish , Armshaw Brennan
Published: August 2021

Many problems that fall in medical domains of inquiry have behavioral components that can be optimized to increase benefits for patients. For example, although surgical intervention is effective in reducing the pain resulting from osteoarthritis of the knee, patients often struggle to regain complete functional use of the joint. In this translational study, we point to some ways in which behavioral contingencies of reinforcement are compromised, making the recovery process more difficult. We also report on the use of surface electromyography (sEMG) with healthy participants to create supplementary contingencies of reinforcement to support the development and maintenance of clinically relevant exercises. The procedures reported provide a proof‐of‐concept and can contribute to an increase in the systematic use of games and feedback in physical rehabilitation in recovery from knee surgery. The results of this translational study suggest an expanded role for applied behavior analysis in the domains of health and medicine.
Polydatin gold nanoparticles potentiate antitumor effect of doxorubicin in Ehrlich ascites carcinoma‐bearing mice
Authors: Samra Yara A. , Abdelghany Amr M. , Zaghloul Randa A.
Published: August 2021

Breast cancer is a leading cause of death. Anticancer treatment such as gold nanoparticles (AuNP) seems highly promising in this regard. Therefore, this study aimed to assess the beneficial effect of doxorubicin (Dox) and polydatin (PD) AuNP in Ehrlich ascites carcinoma (EAC) and the ability of PD–AuNP to protect the heart from Dox's deteriorating effects. EAC was induced in mice. The mice were divided into nine groups: normal, EAC, PD: received PD (20 mg/kg), Dox: received Dox (2 mg/kg), PD–AuNPH: received 10 ppm AuNP of PD, PD–AuNPL: received 5 ppm AuNP of PD, Dox–AuNP: received Dox–AuNP, PD–Dox–AuNP: received PD–Dox–AuNP, AuNP: received AuNP. On the 21st day from tumor inoculation, the mice were sacrificed and tumor and heart tissues were removed. Tumor β‐catenin/Cyclin D1 and p53 were assessed by immunohistochemistry. IL‐6 was determined by enzyme‐linked immunosorbent assay. PD–AuNP and Dox–AuNP showed a significant reduction in tumor volume and weight more than their free forms. Also, PD–AuNP and Dox–AuNP showed markedly less dense tumor cells. β‐catenin and Cyclin D1 were markedly decreased and p53 was highly upregulated by PD–AuNP and Dox–AuNP. Moreover, PD–AuNP and Dox–AuNP have the ability to decrease IL‐6 production. PD–AuNP protected the heart from Dox‐induced severe degeneration. Therefore, PD–AuNP could be a tool to decelerate the progression of breast cancer.
Identification of steroidal saponins from Tribulus terrestris and their in silico docking studies
Authors: Patel Apurva , Bhatt Mital , Soni Anjali , Sharma Preeti
Published: August 2021

Tribulus terrestris is known to possess many pharmacological properties, most notably its anticancer activities, owing to its rich steroidal saponin contents. Even though many reports are available elucidating the anticancer potential of the herb, we, for the very first time have attempted to isolate and identified the active compound present in seed crude saponin extract and confers its in silico docking ability with various cellular targets proteins. High performance thin layer chromatography confirms the presence of active saponins in leaf and seed saponin extracts which were further fractionated by silica gel column chromatography. Fractions collected were assessed for cytotoxicity on human breast cancer cells. High resolution liquid chromatography and mass spectroscopy was employ to identify the active components present in fraction with highest cytotoxicity. Intriguingly, Nautigenin type of steriodal saponin was identified to present in the active fraction of seed extract (SF11) and the identified compound was further analyzed for its in silico docking interaction using PyRx AutodockVina. Docking studies revealed the high binding affinity of Nuatigenin at significant sites with apoptotic proteins Bcl‐2, Bax, caspase‐3, caspase‐8, p53 and apoptosis inducing factor along with cell surface receptors estrogen receptor, projesterone receptor, epidermal growth factor receptor, and human epidermal growth factor receptor‐2. Thus, the conclusions were drawn that saponin fraction of Tribulus terrestis possesses active compounds having anticancer property and specifically, Nuatigenin saponin can be considered as an important therapeutic drug for the breast cancer treatment.
What's in the BAGs? Intrinsic disorder angle of the multifunctionality of the members of a family of chaperone regulators
Authors: Marzullo Liberato , Turco Maria C. , Uversky Vladimir N.
Published: August 2021

In humans, the family of Bcl‐2 associated athanogene (BAG) proteins includes six members characterized by exceptional multifunctionality and engagement in the pathogenesis of various diseases. All of them are capable of interacting with a multitude of often unrelated binding partners. Such binding promiscuity and related functional and pathological multifacetedness cannot be explained or understood within the frames of the classical “one protein–one structure–one function” model, which also fails to explain the presence of multiple isoforms generated for BAG proteins by alternative splicing or alternative translation initiation and their extensive posttranslational modifications. However, all these mysteries can be solved by taking into account the intrinsic disorder phenomenon. In fact, high binding promiscuity and potential to participate in a broad spectrum of interactions with multiple binding partners, as well as a capability to be multifunctional and multipathogenic, are some of the characteristic features of intrinsically disordered proteins and intrinsically disordered protein regions. Such functional proteins or protein regions lacking unique tertiary structures constitute a cornerstone of the protein structure‐function continuum concept. The aim of this paper is to provide an overview of the functional roles of human BAG proteins from the perspective of protein intrinsic disorder which will provide a means for understanding their binding promiscuity, multifunctionality, and relation to the pathogenesis of various diseases.
Risk stratification using sarcopenia status among subjects with metabolic dysfunction‐associated fatty liver disease
Authors: Chun Ho Soo , Kim Mi Na , Lee Jae Seung , Lee Hye Won , Kim Beom Kyung , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Kim Seung Up
Published: August 2021

Background

Sarcopenia is a significant indicator of the severity of non‐alcoholic fatty liver disease. We investigated whether sarcopenia could identify subgroups with different risk of liver fibrosis and atherosclerotic cardiovascular disease (ASCVD) among subjects with metabolic dysfunction‐associated fatty liver disease (MAFLD).

Methods

Subjects from the Korea National Health and Nutrition Examination Survey 2008–2011 were selected (n = 8361). Sarcopenia was defined using the sarcopenia index. Hepatic steatosis was defined as a fatty liver index ≥30. Significant liver fibrosis was defined as a fibrosis‐4 index (FIB‐4) ≥2.67 or the highest quartile of non‐alcoholic fatty liver disease fibrosis score (NFS). High probability of ASCVD was defined as ASCVD risk score >10%.

Results

The mean age was 48.5 ± 15.6 years, and 42.6% of subjects were male. The prevalence of MAFLD was 37.3% (n = 3116 of 8361), and the proportion of sarcopenic subjects was 9.9% among those with MAFLD. After adjusting for confounders, the risk of significant liver fibrosis significantly increased from non‐sarcopenic subjects with MAFLD [odds ratio (OR) = 1.57 by FIB‐4 and 2.13 by NFS] to sarcopenic subjects with MAFLD (OR = 4.51 by FIB‐4 and 5.72 by NFS), compared with subjects without MAFLD (all P < 0.001). The risk for high probability of ASCVD significantly increased from non‐sarcopenic subjects with MAFLD (OR = 1.47) to sarcopenic subjects with MAFLD (OR = 4.08), compared with subjects without MAFLD (all P < 0.001).

Conclusions

The risks of significant liver fibrosis and ASCVD differed significantly according to sarcopenic status among subjects with MAFLD. An assessment of sarcopenia might be helpful in risk stratification among subjects with MAFLD.
Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis
Authors: Takenaka Yukinori , Oya Ryohei , Takemoto Norihiko , Inohara Hidenori
Published: August 2021

Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta‐analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2–51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32–1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88–4.41) for psoas muscle index (PMI), 1.41 (0.87–2.28) for skeletal muscle density (SMD), and 1.43 (1.23–1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08–3.21) for PMI, 1.27 (0.94–1.71) for SMD, and 1.38 (1.11–1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34–0.80 for ORR and OR = 0.45, 95% CI = 0.30–0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15–2.05) for PMI and 0.78 (0.56–1.09) for SMI. The oncologic outcomes associated with melanoma and non‐small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26–3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19–2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51–2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre‐therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo‐controlled D‐Health Trial
Authors: Waterhouse Mary , Sanguineti Emma , Baxter Catherine , Duarte Romero Briony , McLeod Donald S.A. , English Dallas R. , Armstrong Bruce K. , Ebeling Peter R. , Hartel Gunter , Kimlin Michael G. , O'Connell Rachel L. , Pham Hai , van der Pols Jolieke C. , Venn Alison J. , Webb Penelope M. , Whiteman David C. , Neale Rachel E.
Published: August 2021

Background

Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high‐dose vitamin D supplementation reduces risk and incidence of falls.

Methods

We used data from the randomized, double‐blind, placebo‐controlled D‐Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25‐hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3‐month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention‐to‐treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013.

Results

Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) (P‐interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups.

Conclusions

Monthly high‐dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
Cryptococcus extracellular vesicles properties and their use as vaccine platforms
Authors: Rizzo Juliana , Wong Sarah Sze Wah , Gazi Anastasia D. , Moyrand Frédérique , Chaze Thibault , Commere Pierre‐Henri , Novault Sophie , Matondo Mariette , Péhau‐Arnaudet Gérard , Reis Flavia C. G. , Vos Matthijn , Alves Lysangela R. , May Robin C. , Nimrichter Leonardo , Rodrigues Marcio L. , Aimanianda Vishukumar , Janbon Guilhem
Published: August 2021

Whereas extracellular vesicle (EV) research has become commonplace in different biomedical fields, this field of research is still in its infancy in mycology. Here we provide a robust set of data regarding the structural and compositional aspects of EVs isolated from the fungal pathogenic species Cryptococcus neoformans, C. deneoformans and C. deuterogattii. Using cutting‐edge methodological approaches including cryogenic electron microscopy and cryogenic electron tomography, proteomics, and flow cytometry, we revisited cryptococcal EV features and suggest a new EV structural model, in which the vesicular lipid bilayer is covered by mannoprotein‐based fibrillar decoration, bearing the capsule polysaccharide as its outer layer. About 10% of the EV population is devoid of fibrillar decoration, adding another aspect to EV diversity. By analysing EV protein cargo from the three species, we characterized the typical Cryptococcus EV proteome. It contains several membrane‐bound protein families, including some Tsh proteins bearing a SUR7/PalI motif. The presence of known protective antigens on the surface of Cryptococcus EVs, resembling the morphology of encapsulated virus structures, suggested their potential as a vaccine. Indeed, mice immunized with EVs obtained from an acapsular C. neoformans mutant strain rendered a strong antibody response in mice and significantly prolonged their survival upon C. neoformans infection.
Apoptosis‐like death‐inducing property of tachyplesin I in Escherichia coli
Authors: Kwun Min Seok , Lee Dong Gun
Published: August 2021

Antimicrobial peptide (AMP) derived from the horseshoe crab, tachyplesin I (KWCFRVCYRGICYRRCR–NH2), displayed the apparent antimicrobial activity with low cytotoxicity, suggesting its efficacy as an attractive agent but still lacks the understandings regarding its mechanism(s). Hence, the study focused on investigating the antibacterial mode of action of tachyplesin I against Escherichia coli. Based on the reactive oxygen species generation displayed in several antimicrobial effects, the detection of superoxide anion and nitric oxide were verified after tachyplesin I treatment. Substantial increment of two molecules was followed by the imbalance in intracellular ion concentration, noticeably magnesium and calcium. The series of stages led to hydroxyl radical generation with reduced glutathione, followed by damage in DNA due to oxidative stress. Eventually, the apoptosis‐like death in E. coli was monitored in DNA fragmentation‐dependent manner due to the tachyplesin I treatment, verified by membrane depolarization, caspase‐like protein activation, and phosphatidylserine exposure. Accordingly, tachyplesin I induces apoptosis‐like death in E. coli, suggesting the potential of being a candidate for regulating bacterial infection.
Contributions of the climate regime shift and historical global warming to explosive cyclone activity around Japan according to large‐ensemble simulations
Authors: Tsukijihara Takumi , Kawamura Ryuichi
Published: August 2021

Using the Database for Policy Decision‐Making for Future Climate Change (d4PDF), this study examined the impact of a tropical climate regime shift around 1998/1999 on explosive cyclone activity around Japan in boreal winter, highlighting cyclones moving along the Kuroshio Current (KC cyclones), especially northward‐migrating (N‐type, as defined in Tsukijihara et al., 2019) KC cyclones. Wave‐train patterns along the Asian jet affect the track and rapid development of N‐type cyclones, and the frequency of the top 10% of pronounced wave‐train patterns using a teleconnection index (NI10%) has increased since 1998/1999. Tropical precipitation in the region close to the Bay of Bengal increased with the climate regime shift, leading to the increased frequency of NI10%. The downstream development of wave packets tends to form a ridge with a barotropic structure east of Japan that is able to force the northward shift of the KC cyclone. In reality, there are high correlations between the inter‐annual variations in the ensemble mean frequencies of NI10%, N‐type cyclones, and tropical precipitation around the Bay of Bengal, and all three indices have increased since 1998/1999. Furthermore, the above results are nearly the same in both historical and non‐warming experiments, indicating that recent changes in the frequency of N‐type cyclones are not directly related to historical global warming.
Poleward migration of tropical cyclones and its related typological characteristics of seasonal maximum precipitation in China
Authors: Wu Dian , Jun Changhyun , Kim Jong‐Suk , Xiong Lihua , Chen Jie
Published: August 2021

Tropical cyclones (TCs) influence extreme rainfall events. However, changes in TCs caused by their poleward migration and subsequent impacts on extreme rainfall are yet to be adequately explored. In this study, the long‐term trends of TCs and typological characteristics of TC‐induced rainfall were analysed. Daily rainfall data were obtained from 759 Chinese stations and TC data were obtained in the Northwest Pacific (NWP) regions from 1961 to 2017. From May to October of each year, the TC‐induced rainfall was separated from the total rainfall data and spatiotemporal distribution patterns of TC‐induced rainfall were identified. The amount and frequency of TC‐induced rainfall decrease from the coastal inland. The TCs migrate northward, leading to a decrease (increase) in their activities south (north) of 20°N, respectively. In the South China Sea, TC activity is decreasing. The number of TC landfall events is decreasing (increasing) in the Pearl River basin (Southeast River basin). Furthermore, nonstationary increasing trends in the Pearl River and Southeast basins account for 41.7 and 62.9%, respectively, whereas the decreasing trends account for 30.6 and 14.3%, respectively. The Southeast River basin may face more TC‐induced extreme rainfall in the future. The results can provide information for water resource management and flood disaster warning systems in China, especially in the southeast.
Global population‐weighted degree‐day projections for a combination of climate and socio‐economic scenarios
Authors: Spinoni Jonathan , Barbosa Paulo , Füssel Hans‐Martin , McCormick Niall , Vogt Jürgen V. , Dosio Alessandro
Published: August 2021

The projected global temperature increase in the 21st century is expected to have consequences on energy consumption due to increase (decrease) in energy demand to cool (heat) the built environments. Such increase (decrease) also depends on the number of end users for such energy, thus it is crucial to include population into the analyses. This study presents population‐weighted (w) cooling (CDD), heating (HDD), and energy (EDD) degree‐day projections at global, regional, and local scales for the 21st century. We used a large ensemble of high‐resolution (0.44°) climate simulations from the COordinated Regional‐climate Downscaling EXperiment (CORDEX) to compute degree‐days for baseline (1981–2010) and global warming levels (GWLs from 1.5°C to 4°C), based on two representative concentration pathways. We used population projections from the NASA‐SEDAC datasets, driven by five socio‐economic scenarios (SSPs). The progressive increase in CDD outbalances the decrease in HDD in Central and South America, Africa, and Oceania and the opposite situation is likely to occur in North America, Europe, and Asia; at global scale, they are balanced. However, if results are weighted according to population, the increase in wCDD outbalances the decrease in wHDD almost everywhere for most GWLs and SSPs. Few regions show a decreasing tendency in wEDD at high GWLs for all SSPs: central Europe, northwestern, northeastern, and eastern Asia. Globally, wEDD are likely to double at 2°C compared to 1981–2010 independently of the SSP. Under the worst‐case scenario (SSP3), at 4°C wCDD are approximately 380% higher and wHDD approximately 30% lower than in the recent past, leading to an increase in wEDD close to 300%.
Trends in probabilities of temperature records in the non‐stationary climate of South Africa
Authors: McBride Charlotte M. , Kruger Andries C. , Dyson Liesl
Published: August 2021

The temporal and spatial distribution of the frequency of breaking highest and lowest daily maximum and minimum temperature records over the period of 1951–2019 has been investigated for South Africa. Temperature records are station specific and defined as either larger or smaller than any previous values in a time series of specific year‐days. Daily maximum and minimum temperatures from homogenized time series of 25 weather stations in South Africa were analysed. Aspects considered to influence the frequency of record‐breaking events were the warming trend and variance. The study found that the record‐breaking frequencies of the highest daily maximum (high Tmax) and some high daily minimum temperature (high Tmin) records were higher than the theoretically expected number in a stationary climate. This was particularly apparent near the end of the analysis period. The ratio of highest maximum to lowest minimum temperature records was almost an equal 1:1 ratio near the start of the analysis period and increased to a about 4:1 in the last decade of the period. Focusing on the last decade, that is, 2010–2019 the study found that there is a different spatial pattern between the occurrence of high Tmax and high Tmin records. For high Tmax records the highest number were mostly recorded by stations over the central parts of the country (e.g., Kimberley, Glen College and Bloemfontein). In contrast, the highest number of high Tmin records were less confined spatially. Even when considering the general warming due to climate change, many more high temperature records are broken than expected in certain regions and on average. We deduce that the higher than expected numbers of high Tmax and high Tmin records in the latter part of the analysis period were mainly due to the variability in the warming trend with acceleration in the last decade.
In vitro comparison of root surface roughness and bacterial adhesion following treatment with three different instruments
Authors: Haroon Farah , Gregory Richard L. , Hara Anderson , Blanchard Steven B. , Hamada Yusuke
Published: August 2021

Background

A novel device, piezoelectric 11 Gracey curet tip, reportedly combines benefits of a piezoelectric device and manual curet. The primary objective of this study was to compare root surface roughness outcomes between traditional manual curets and piezoelectric devices, as compared with this novel device. The secondary aim was to assess the level of adhesion of Streptococcus mutans on the root surface after instrumentation.

Methods

The groups consisted of the following: 1) Gracey curet; 2) piezoelectric scaler; 3) piezoelectric 11 Gracey curet tip; and 4) untreated control. Root specimens were obtained from extracted human teeth and randomly assigned to each group. Surface roughness measurements (Ra and Rz) were taken with a profilometer before and after instrumentation. After instrumentation, root specimens were inoculated with S. mutans and biofilm was dislodged. Various dilutions of resuspended biofilm were incubated on blood agar plates and colony forming units (CFU) values were measured.

Results

The experimental device resulted in significantly lower Ra and Rz compared with other groups (P < 0.01), and the Gracey curet was significantly lower than the piezoelectric tip and untreated control (P < 0.05). The Gracey curet and experimental device tip had significantly lower CFU values compared with the control (P < 0.05). There were no significant CFU value differences between the Gracey curet and both the piezoelectric and experimental device tips. There were no significant CFU differences between piezoelectric tip and both experimental device and control. There was no correlation between Ra and CFU values for Gracey curet, piezoelectric tip, or the control. However, correlation between Ra values and CFU approached significance for the experimental device (correlation = 0.66, P = 0.05).

Conclusions

Piezoelectric 11 Gracey curet tip is effective at resulting in a significantly smoother surface compared with traditional piezoelectric and hand instruments. CFU values with piezoelectric 11 Gracey curet tip were significantly lower than non‐instrumented surfaces, but there were no significant differences compared with conventional methods.
Integrated nutrient management improves soil organic matter and agronomic sustainability of semiarid rainfed Inceptisols of the Indo‐Gangetic Plains
Authors: Srinivasarao Ch. , Singh S. P. , Kundu Sumanta , Abrol Vikas , Lal Rattan , Abhilash P. C. , Chary G. R. , Thakur Pravin B. , Prasad J. V. N. S. , Venkateswarlu B.
Published: August 2021

Background

Climate and management practices impact the soil organic carbon (SOC) stocks of agricultural soils. Especially under the semiarid climate of India, organic matter is rapidly decomposed, and imbalanced nutrient input further exacerbates its depletion, thus facilitating the decline in soil quality and crop yields. Improving SOC contents through integrated nutrient management (INM), that is, conjunctive use of organic and chemical sources of nutrients, could ameliorate soil health and sustain crop yields.

Aim

To assess the potential of the INM approach to enhance the SOC status, soil quality, crop production, and drought adaptation of pearl millet under rainfed conditions.

Methods

Nutrient inputs were supplied through mineral fertilizers, organic manures, and a combination of both. SOC sequestration, sustainable yield index, plant‐available N, P, K, and water, bulk density, and KMnO4‐oxidizable C were estimated.

Results

Higher SOC sequestration rate (0.50 and 0.48 Mg ha−1 y−1 in 50% N (fertilizer) + 50% N (farmyard manure), and 50% N (fertilizer) + 50% N (crop residue), respectively) and significant increase in soil fertility were recorded in organically amended treatments. Improvement of 1 Mg ha−1 of SOC stock in the root zone (0.4 m depth) reduced the severity of drought and increased the yield by 38 kg ha−1. Plots under organic amendments suffered less yield losses under short‐duration droughts, but this positive effect could only be exploited when the rainfall deficit was up to 25%.

Conclusion

Managements that add up to 1.2 Mg ha−1 y−1 SOC are adaptive and climate‐resilient strategies in dry semiarid degraded Inceptisols of the Indo‐Gangetic Plains.
Late Holocene in central Brazil: vegetation changes and humidity variability in a tropical wetland
Authors: SABINO SHIRLEY MARIA LIMA , CASSINO RAQUEL FRANCO , GOMES MAKÊNIA OLIVEIRA SOARES , SANT'ANNA ENEIDA MARIA ESKINAZI , ROCHA AUGUSTIN CRISTINA HELENA RIBEIRO , DE OLIVEIRA DIEGO ALVES
Published: August 2021

The Pandeiros wetland is a high biodiversity ecosystem located within a semiarid region of the Cerrado biome, a neotropical savanna. This large wetland is of key importance for ecological and hydrological balance in central Brazil and for the conservation of the Cerrado fauna and flora. In this study, we present the first palaeoecological investigation of the Pandeiros wetland based on pollen analysis of a palm swamp sediment core encompassing the Late Holocene. Our results show that the wetland was subject to multicentennial‐scale oscillations in water availability during the Late Holocene; in particular, higher local humidity was documented between 4100 and 3100 cal a
bp and from 2600 to 1000 cal a
bp, and two events of drier local conditions occurred at approximately 2900 and 900 cal a
bp. Our results also indicate a general decreasing trend in arboreal density in the Pandeiros River Basin from the beginning of the Late Holocene to the present, with the greatest expansion of dry forest occurring between 3600 and 3100 cal a
bp.