bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive performance evaluation of stormwater management measures for sponge city construction: A case study in Gui'an New District, China
Authors: Yao Yichen , Hu Caihong , Liu Chengshuai , Yang Fan , Ma Bingyan , Wu Qiang , Li Xinan , Soomro Shan‐e‐hyder
Published: July 2022

Climate change and rapid urbanization have increased pressure on drainage systems, posing new challenges to preventing and controlling urban waterlogging. In 2013, China proposed the Sponge City, a strategic measure for urban waterlogging control. This study quantifies the effects of stormwater management measures in runoff reduction for different levels of rainfall and conducts a one‐dimensional visual analysis of urban waterlogging risks. At the same time, the best cost‐effective scheme is determined based on life‐cycle cost, analytic hierarchy process, and regret decision theory. The results showed stormwater management measures could realize the function of runoff control and waterlogging prevention, especially under low precipitation. However, these measures were still not enough to eliminate waterlogging risk. Combined measures have stronger runoff control capabilities than single measures. Considering economic, environmental, and operational impacts comprehensively, the combined measures of bio‐retention (BR), permeable pavement (PP), and green roof (GR) were determined as the best cost‐effective scheme because of the lowest regret value. The proposed method is helpful to provide reference and decision‐making basis for the construction of sponge cities in the future.
Perception of atrial fibrillation symptoms: Impact on quality of life and treatment in older adults
Authors: Abu Hawa O. , Wang Weijia , Otabil Edith M. , Saczynski Jane S. , Mehawej Jordy , Mishra Ajay , Tisminetzky Mayra , Blanchard Gary , Gurwitz Jerry H. , Goldberg Robert J. , McManus David D.
Published: July 2022

Background

In managing older adults with atrial fibrillation (AF), their symptomatology impacts their well‐being and may inform treatment decision‐making. We examined AF symptom perception, its impact on quality of life (QoL), and its relation to treatment strategies in older adults with AF.

Methods

Data were obtained from older adults with AF enrolled in a multicenter study conducted at clinic sites in Massachusetts and Georgia between 2016 and 2018. Participants were stratified into three age groups: 65–74 (youngest–old), 75–84 (middle–old), and ≥85 (oldest). Perception of AF symptoms was assessed by participant self‐report during their clinic visit and at study enrollment by the Atrial Fibrillation Effect on Quality‐of‐Life Questionnaire which assessed cardiac‐specific and non‐specific, non‐cardiac AF symptoms and their impact on QoL. Treatment strategies (rate or rhythm control) utilized were ascertained from electronic medical records.

Results

Among the 1184 participants (mean age 75 years, 48% women, 86% Non‐Hispanic White), 51% were aged 65–74 years, 36% were 75–84 years, and 13% were ≥ 85 years. The most commonly reported AF symptoms were non‐specific, non‐cardiac symptoms (fatigue, dyspnea, lightheadedness) with similar prevalence and impact on QoL in all age groups. Cardiac‐specific AF symptoms (palpitations, irregular heartbeat, pause in heart activity) were less prevalent, but most commonly reported by the youngest participants (65–74 years), who endorsed considerable impact of these symptoms on their QoL. Overall, those who reported experiencing any AF symptoms during their clinic visit were more likely to have received rhythm compared with rate control (OR: 1.56; 95% CI: 1.18–2.04) with similar findings for all age groups except those aged ≥85 years.

Conclusions

Our findings suggest a high prevalence of non‐specific, non‐cardiac symptoms among older adults with AF and that cardiac‐specific AF symptoms may exert considerable impact on their QoL. The presence of any AF symptoms may drive more rhythm control in a majority of older adults.
Effect of leukoreduction on inflammation in critically ill dogs receiving red blood cell transfusions: A randomized blinded controlled clinical trial
Authors: Claus Melissa A. , Poh Denise , Smart Lisa , Purcell Sarah L. , Boyd Corrin J. , Sharp Claire R.
Published: July 2022

Background

Prestorage leukoreduction of red blood cell (RBC) bags prevents accumulation of pro‐inflammatory mediators and experimentally attenuates post‐transfusion inflammation in healthy dogs. However, the effect of leukoreduction on post‐transfusion inflammation in critically ill dogs is unclear.

Hypothesis

Dogs transfused with leukoreduced (LR) RBC will have lower concentrations of leukocytes, interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1), and C‐reactive protein (CRP) within 24 hours of post‐transfusion compared to dogs transfused with nonleukoreduced (NLR) RBC.

Animals

Sixty‐one RBC‐transfused dogs (LR = 34, NLR = 27).

Methods

Randomized, blinded, controlled preliminary clinical trial. Blood bag processing was randomized to create identically appearing LR and NLR bags. Group allocation occurred with transfusion of the oldest compatible RBC bag. Blood samples were collected pretransfusion and at 8 and 24 hours post‐transfusion for leukocyte count, IL‐6, IL‐8, MCP‐1, and CRP. Data were analyzed on an intention‐to‐treat basis using linear mixed effects models. Significance was set at P < .05.

Results

No significant differences were found between groups in concentrations of leukocytes (P = .93), IL‐6 (P = .99), IL‐8 (P = .75), MCP‐1 (P = .69), or CRP (P = .18) over time. Eleven LR dogs (32%) and 4 NLR dogs (15%) were euthanized in the hospital (P = .14). No natural deaths occurred.

Conclusions and Clinical Importance

No differences in inflammation biomarker concentrations were detected over time between dogs transfused with LR or NLR RBC, but heterogeneity likely hampered the ability to detect a difference with this sample size. The novel randomization and enrollment protocol was successfully implemented across 2 participating institutions and will be easily scaled up for a future multicenter clinical trial.
Designing the learning of intraprofessional collaboration among medical residents
Authors: Looman Natasja , de Graaf Jacqueline , Thoonen Bart , van Asselt Dieneke , de Groot Esther , Kramer Anneke , Scherpbier Nynke , Fluit Cornelia
Published: July 2022

Background

To preserve quality and continuity of care, collaboration between primary‐care and secondary‐care physicians is becoming increasingly important. Therefore, learning intraprofessional collaboration (intraPC) requires explicit attention during postgraduate training. Hospital placements provide opportunities for intraPC learning, but these opportunities require interventions to support and enhance such learning. Design‐Principles guide the design and development of educational activities when theory‐driven Design‐Principles are tailored into context‐sensitive Design‐Principles. The aim of this study was to develop and substantiate a set of theory‐driven and context‐sensitive Design‐Principles for intraPC learning during hospital placements.

Methods

Based on our earlier research, we formulated nine theory‐driven Design‐Principles. To enrich, refine and consolidate these principles, three focus group sessions with stakeholders were conducted using a Modified Nominal Group Technique. Next, two work conferences were conducted to test the feasibility and applicability of the Design‐Principles for developing intraPC educational activities and to sharpen the principles into a final set of Design‐Principles.

Results

The theoretical Design‐Principles were discussed and modified iteratively. Two new Design‐Principles were added during focus group 1, and one more Design‐Principle was added during focus group 2. The Design‐Principles were categorised into three clusters: (i) Culture: building collaborative relations in a psychologically safe context where patterns or feelings of power dynamics between primary and secondary care physicians can be discussed; (ii) Connecting Contexts: making residents and supervisors mutually understand each other's work contexts and activities; and (iii) Making the Implicit Explicit: having supervising teams act as role models demonstrating intraPC and continuously pursuing improvement in intraPC to make intraPC explicit. Participants were unanimous in their view that the Design‐Principles in the Culture cluster were prerequisites to facilitate intraPC learning.

Conclusion

This study led to the development of 12 theory‐driven and context‐sensitive Design‐Principles that may guide the design of educational activities to support intraPC learning during hospital placements.
Actin‐bundling protein fimbrin regulates pathogenicity via organizing F‐actin dynamics during appressorium development in Colletotrichum gloeosporioides
Authors: Zhang Yi , An Bang , Wang Wenfeng , Zhang Bei , He Chaozu , Luo Hongli , Wang Qiannan
Published: July 2022

Anthracnose caused by Colletotrichum gloeosporioides leads to serious economic loss to rubber tree yield and other tropical crops. The appressorium, a specialized dome‐shaped infection structure, plays a crucial role in the pathogenesis of C. gloeosporioides. However, the mechanism of how actin cytoskeleton dynamics regulate appressorium formation and penetration remains poorly defined in C. gloeosporioides. In this study, an actin cross‐linking protein fimbrin homologue (CgFim1) was identified in C. gloeosporioides, and the knockout of CgFim1 led to impairment in vegetative growth, conidiation, and pathogenicity. We then investigated the roles of CgFim1 in the dynamic organization of the actin cytoskeleton. We observed that actin patches and cables localized at the apical and subapical regions of the hyphal tip, and showed a disc‐to‐ring dynamic around the pore during appressorium development. CgFim1 showed a similar distribution pattern to the actin cytoskeleton. Moreover, knockout of CgFim1 affected the polarity of the actin cytoskeleton in the hyphal tip and disrupted the actin dynamics and ring structure formation in the appressorium, which prevented polar growth and appressorium development. The CgFim1 mutant also interfered with the septin structure formation. This caused defects in pore wall overlay formation, pore contraction, and the extension of the penetration peg. These results reveal the mechanism by which CgFim1 regulates the growth and pathogenicity of C. gloeosporioides by organizing the actin cytoskeleton.
Videolaryngoscopes versus direct laryngoscopes in children: Ranking systematic review with network meta‐analyses of randomized clinical trials
Authors: de Carvalho Clístenes C. , Regueira Stéphanie L. P. A. , Souza Ana Beatriz S. , Medeiros Lucas M. L. F. , Manoel Marielle B. S. , da Silva Danielle M. , Santos Neto Jayme M. , Peyton James
Published: July 2022

Background

Videolaryngoscopes improve tracheal intubation in adult patients, but we currently do not know whether they are similarly beneficial for children. We designed this ranking systematic review to compare individual video and direct laryngoscopes for efficacy and safety of orotracheal intubation in children.

Methods

We searched PubMed and five other databases on January 27, 2021. We included randomized clinical trials with patients aged ≤18 years, comparing different laryngoscopes for the outcomes: failed first intubation attempt; failed intubation within two attempts; failed intubation; glottic view; time for intubation; complications. In addition, we assessed the quality of evidence according to GRADE recommendations.

Results

We included 46 studies in the meta‐analyses. Videolaryngoscopy reduced the risk of failed first intubation attempt (RR = 0.43; 95% CI: 0.31–0.61; p = .001) and failed intubation within two attempts (RR = 0.33; 95% CI: 0.33–0.33; p < .001) in children aged <1 year. Videolaryngoscopy also reduced the risk of major complications in both children aged <1 year (RR = 0.33; 95% CI: 0.12–0.96; p = .046) and children aged 0–18 years (RR = 0.40; 95% CI: 0.25–0.65; p = .002). We did not find significant difference between videolaryngoscopy and direct laryngoscopy for time to intubation in children aged <1 year (MD = −0.95 s; 95% CI: −5.45 to 3.57 s; p = .681), and children aged 0–18 years (MD = 1.65 s; 95% CI: −1.00 to 4.30 s; p = .222). Different videolaryngoscopes were associated with different performance metrics within this meta‐analysis. The overall quality of the evidence ranged from low to very low.

Conclusion

Videolaryngoscopes reduce the risk of failed first intubation attempts and major complications in children compared to direct laryngoscopes. However, not all videolaryngoscopes have the same performance metrics, and more data is needed to clarify which device may be better in different clinical scenarios. Additionally, care must be taken while interpreting our results and rankings due to the available evidence's low or very low quality.
Seed germination traits and dormancy classification of 27 species from a degraded karst mountain in central Yunnan–Guizhou Plateau: seed mass and moisture content correlate with germination capacity
Authors: Wang J. , Wang X.Y. , Pan W. , Li J.Y. , Xue L. , Li S.
Published: July 2022

In degraded karst ecosystem, vegetation restoration efforts almost exclusively rely on planted seedlings, but this is not effective to maintain community diversity and resilience. As seed functional traits, seed dormancy and germination are key to community assembly. Unfortunately, these elements are commonly overlooked in restoring degraded ecosystems.

This work classifies seed dormancy of 27 species with different life forms that are common on a degraded karst mountain. We examined the effects of temperature regime and light conditions on percentage germination and assessed the relationships between seed traits and germination index using a partial least squares regression (PLSR).

Approximately 48% of the investigated species had physiological dormancy, 37% were non‐dormant, 7% had morphophysiological dormancy, 4% had morphological dormancy and 4% had physical dormancy. We found that 94% (15 out of 16) species had maximum germination in warm temperature regimes (20/13 and 25/18 °C), while the remaining species required cool temperatures (10/4 °C). PLSR analysis indicated a significant positive correlation between seed mass and T50m (time to 50% final germination), and a negative correlation between seed moisture content and percentage germination.

Our findings indicate that seed traits are important factors in seed‐based restoration practice. F. esculentum, O. opipara, P. fortuneana and S. salicifolia are recommended for direct seeding during the early rainy season to restore seriously degraded lands in subtropical karst regions.
The myth of economic incentives around the debate on the design of optimal pension systems: A survival analysis for the Argentine case
Authors: Geri Milva , Villareal Fernanda
Published: July 2022

From a panel of administrative data of contributors to the Argentine pension system, a survival analysis was carried out to compare the time in months until contributor status is lost for individuals who reach the minimum retirement age. The analysis involves two periods: one where the fully funded scheme was in force and the other with the pure pay‐as‐you‐go scheme in effect. It is observed that the survival curve of the contributor status during the second period is always above that in the first one, indicating that the probability of maintaining this status was always higher during the second period. Likewise, it was found that belonging to the cohort/group of the first period is significant in explaining the risk of losing contributor status, even controlling for other relevant variables. This result contrasts with the predictions of the World Bank about the best incentives that the fully funded scheme would generate for the supply of formal labor.

Related Articles

Angelaki, Marina, and Leandro N. Carrera. 2015. “Radical Pension Reforms after the Crisis: A Comparative Analysis of Argentina and Greece.”Politics & Policy43(3): 378–400.https://doi.org/10.1111/polp.12117.

Hazakis, Konstantinos J. 2015. “The Political Economy of Economic Adjustment Programs in the Eurozone: A Detailed Policy Analysis.”Politics & Policy43(6): 822–54.https://doi.org/10.1111/polp.12141.

Jakee, Keith, and Keith Stacy. 2021. “Revisiting Pension Reform in Sweden: The Role of Corporatism (and Why it Matters).”Politics & Policy49(3): 651–81.https://doi.org/10.1111/polp.12405.
Identification and characterization of pathogenicity of Lelliottia nimipressuralis causing soft rot of Codonopsis pilosula (dangshen) roots in China
Authors: Zhao Xia , Tian Yuan , Yue Liang , Liu Yang , Yan Yufei , Zhou Qin , Wang Yun , Zhang Yubao , Wang Ruoyu
Published: July 2022

The roots of Codonopsis pilosula, a crucial ingredient in Chinese medicine, are prone to soft rot disease soon after transplanting seedlings in the second year. This almost always causes severe losses in yield at harvest, with severe economic consequences for farmers of this perennial vine. However, the pathogens involved remain understudied, although some gram‐negative bacteria of the Enterobacteriaceae family are well‐known pathogens of soft rot in many other plants. Here, the isolate B5‐2‐1‐30 was suspected of being a key pathogen of C. pilosula in China according to counts of bacteria from diseased, healthy and adjacent tissues of roots. Results of morphological and phylogenetic analyses, including microscopic observations, in addition to a multilocus sequence analysis (MLSA) of the concatenated partial 16S rDNA, rpoB, atpD and gyrB genes, revealed that this isolate belongs to Lelliottia nimipressuralis. In vitro and in vivo pathogenicity tests showed that L. nimipressuralis B5‐2‐1‐30 could cause root soft rot in seedlings of C. pilosula, with symptoms similar to those observed in the field. Further experiments suggested the typical symptoms of softened rotting roots and wilting shoots arose from phloem necrosis and vessel plugging, as inferred by observed anatomical characteristics of roots, providing clues for elucidating the infection mechanism of phytopathogens in L. nimipressuralis.
Do employers avoid hiring workers from poor neighborhoods? Experimental evidence from the real labor market*
Authors: Carlsson Magnus , Eriksson Stefan
Published: July 2022

We investigate whether employers avoid hiring workers who live in neighborhoods with low socio‐economic status and/or with long commuting times. In a large‐scale field experiment in the Swedish labor market, we sent more than 4,000 fictitious résumés, with randomly assigned information about the applicants' residential locations, to firms with advertised vacancies. Our findings show that commuting time has a negative effect on the likelihood of being contacted by an employer, while the socio‐economic status of a neighborhood does not appear to be important. These results offer guidance for policymakers who are responsible for reversing segregation patterns.
Description of the HLA‐B*41:01:08 allele: First identified in a Brazilian individual
Authors: Vianna Romulo , Secco Danielle , Lopes Giovanna , Santos Angela , Porto Luís Cristóvão
Published: July 2022

The novel HLA‐B*41:01:08 allele, first described in a potential bone marrow donor from Brazil.
Transplanted organoids empower human preclinical assessment of drug candidate for the clinic
Authors: Westerling-Bui Amy D. , Fast Eva Maria , Soare Thomas W. , Venkatachalan Srinivasan , DeRan Michael , Fanelli Alyssa B. , Kyrychenko Sergii , Hoang Hien , Corriea Grinal M. , Zhang Wei , Yu Maolin , Daniels Matthew , Malojcic Goran , Pan-Zhou Xin-Ru , Ledeboer Mark W. , Harmange Jean-Christophe , Emani Maheswarareddy , Tibbitts Thomas T. , Reilly John F. , Mundel Peter
Published: July 2022

Pharmacodynamic (PD) studies are an essential component of preclinical drug discovery. Current approaches for PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PD studies using transplanted, perfused human kidney organoids. We performed pharmacokinetic (PK) studies with GFB-887, an investigational new drug now in phase 2 trials. Orally dosed GFB-887 to athymic rats that had undergone organoid transplantation resulted in measurable drug exposure in transplanted organoids. We established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates feasibility of using transplanted human organoids in preclinical PD studies with an investigational new drug, empowering organoids to revolutionize drug discovery.
The seeds and homogeneous nucleation of photoinduced nonthermal melting in semiconductors due to self-amplified local dynamic instability
Authors: Liu Wen-Hao , Luo Jun-Wei , Li Shu-Shen , Wang Lin-Wang
Published: July 2022

Laser-induced nonthermal melting in semiconductors has been studied over the past four decades, but the underlying mechanism is still under debate. Here, by using an advanced real-time time-dependent density functional theory simulation, we reveal that the photoexcitation-induced ultrafast nonthermal melting in silicon occurs via homogeneous nucleation with random seeds originating from a self-amplified local dynamic instability. Because of this local dynamic instability, any initial small random thermal displacements of atoms can be amplified by a charge transfer of photoexcited carriers, which, in turn, creates a local self-trapping center for the excited carriers and yields the random nucleation seeds. Because a sufficient amount of photoexcited hot carriers must be cooled down to band edges before participating in the self-amplification of local lattice distortions, the time needed for hot carrier cooling is the response for the longer melting time scales at shorter laser wavelengths. This finding provides fresh insights into photoinduced ultrafast nonthermal melting.
Direct search for dark matter axions excluding ALP cogenesis in the 63- to 67-μeV range with the ORGAN experiment
Authors: Quiskamp Aaron , McAllister Ben T. , Altin Paul , Ivanov Eugene N. , Goryachev Maxim , Tobar Michael E.
Published: July 2022

The standard model axion seesaw Higgs portal inflation (SMASH) model is a well-motivated, self-contained description of particle physics that predicts axion dark matter particles to exist within the mass range of 50 to 200 micro–electron volts. Scanning these masses requires an axion haloscope to operate under a constant magnetic field between 12 and 48 gigahertz. The ORGAN (Oscillating Resonant Group AxioN) experiment (in Perth, Australia) is a microwave cavity axion haloscope that aims to search the majority of the mass range predicted by the SMASH model. Our initial phase 1a scan sets an upper limit on the coupling of axions to two photons of ∣
g
aγγ
∣ ≤ 3 × 10
−12
per giga–electron volts over the mass range of 63.2 to 67.1 micro–electron volts with 95% confidence interval. This highly sensitive result is sufficient to exclude the well-motivated axion-like particle cogenesis model for dark matter in the searched region.
Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents
Authors: Cho Frances S. , Vainchtein Ilia D. , Voskobiynyk Yuliya , Morningstar Allison R. , Aparicio Francisco , Higashikubo Bryan , Ciesielska Agnieszka , Broekaart Diede W. M. , Anink Jasper J. , van Vliet Erwin A. , Yu Xinzhu , Khakh Baljit S. , Aronica Eleonora , Molofsky Anna V. , Paz Jeanne T.
Published: July 2022

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown. Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury. In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury. Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway. Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.
Functional and Metagenomic Evaluation of Ibezapolstat for Early Evaluation of Anti-Recurrence Effects in Clostridioides difficile Infection
Authors: McPherson Jacob , Hu Chenlin , Begum Khurshida , Wang Weiqun , Lancaster Chris , Gonzales-Luna Anne J. , Loveall Caroline , Silverman Michael H. , Alam M. Jahangir , Garey Kevin W.
Published: July 2022

Reduction of
Clostridioides difficile
infection (CDI) recurrence is an essential endpoint for CDI-directed antibiotic development that is often not evaluated until Phase III trials. The purpose of this project was to use a functional and metagenomic approach to predict the potential anti-CDI recurrence effect of ibezapolstat, a DNA polymerase IIIC inhibitor, in clinical development for CDI.
In VivoProfiling of Individual Multiciliated Cells during Acute Influenza A Virus Infection
Authors: Hamele Cait E. , Russell Alistair B. , Heaton Nicholas S.
Published: July 2022

Influenza A virus poses a significant threat to public health, and each year, millions of people in the United States alone are exposed to the virus. We do not currently, however, fully understand why some individuals clear the infection asymptomatically and others become severely ill.
Symptomatic and Asymptomatic Transmission of SARS-CoV-2 in K-12 Schools, British Columbia, Canada April to June 2021
Authors: Choi Alexandra , Mâsse Louise C. , Bardwell Samantha , Kayda Iryna , Zhao Yanjie , Xu Yang Xin Zi , Markarian Ani , Coombs Daniel , Macdonald Adrienne , Watts Allison W. , Dhillon Nalin , Irvine Michael , O’Reilly Collette , Lavoie Pascal M. , Goldfarb David M.
Published: July 2022

There is concern that schools may be a setting where asymptomatic infections might result in significant “silent” transmission of SARS-CoV-2, particularly after the emergence of more transmissible variants of concern. After the programmatic implementation of a strategy of asymptomatic testing of close COVID-19 contacts as part of contact tracing in the school setting, the majority of the secondary cases were still found to have occurred in home or social contacts.
A newly defined, long-lived Paleozoic intra-oceanic arc in the South Tianshan (NW China): Implications for multiple accretionary tectonics in the southern Altaids
Authors: Gao Limin , Xiao Wenjiao , Tan Zhou , Wang Xinshui , Guo Yuhong
Published: July 2022

The South Tianshan Orogenic Belt marks the final assembly of the southern Altaids and the Karakum-Tarim Cratons. Integrated petrological, geochemical, and geochronological studies were carried out on the Akeyazi high-alumina basaltic lavas (HABs) and their host sandstones from the southern margin of the Central Tianshan Block. Given their relative high alumina contents (Al2O3 > 16 wt%) and geochemical similarity to basalts from modern arcs (e.g., Aleutian, Kamchatka, Izu, and Honshu arc), the Akeyazi basaltic lavas are classified as HABs. The Akeyazi HABs are distinguished by strong enrichment in large ion lithophile elements (LILE) and negative Nb-Ta anomalies. Furthermore, their mid-oceanic ridge basalt (MORB)-like Sr-Nd-Hf (87Sr/86Sr(i) ~0.705766, εNd(t) ~+2.5, εHf(t) ~+9.5), along with arc-like trace element patterns, indicate a petrogenesis derived from a mantle wedge metasomatized by pelagic, sediment-derived melts (2%–5% melts mixed, as confirmed by melt modeling). Zircon U-Pb ages of Akeyazi HABs and associated arc-related gabbros suggest that they were mainly erupted during ca. 415 Ma. Moreover, host sandstones of Akeyazi HABs exhibit a unimodal distribution with a peak at 480–410 Ma in the detrital zircon spectrum, which is notably distinct from those of the Central Tianshan Block, South Tianshan Accretionary Complex, and North Tarim Craton, each of which is multimodal. The maximum depositional age (MDA) of the meta-sandstones is 351.0 ± 4.3 Ma, with the weighted average of three oldest Paleozoic grains at 502 ± 26 Ma. Collectively, our data, for the first time, discloses an intra-oceanic arc setting from ca. 502–351 Ma during the northward subduction of the South Tianshan Ocean, which further reveals the history of multiple episodes of accretion in the southern Altaids.
Mesoproterozoic oxygenation event: From shallow marine to atmosphere
Authors: Xie Baozeng , Zhu Jian-ming , Wang Xiangli , Xu Dongtao , Zhou Limin , Zhou Xiqiang , Shi Xiaoying , Tang Dongjie
Published: July 2022

Oxygen availability is crucial for the evolution of eukaryotes in geological history, but the redox conditions of the mid-Proterozoic atmospheric-oceanic system remain vigorously debated. Previous geochemical studies suggested a very low mid-Proterozoic atmospheric oxygen level of probably below 0.1%–1% of the present atmospheric level (PAL) with weakly oxygenated surface ocean, which may have suppressed the early evolution of eukaryotes in the ocean. A recent study, however, revealed a pulsed oxygenation event that was recorded in shallow marine carbonate of the middle Gaoyuzhuang Formation (at ca. 1.57 Ga, North China) with atmospheric pO2 of up to ≥4% PAL based on iodine speciation. This event is associated with the earliest known multi-cellular eukaryotic fossils. To elucidate whether this pulsed oxygenation was limited to shallow local seawaters or could also reflect an increase in atmospheric oxygen, chromium (Cr), and carbonate-associated sulfate (CAS), sulfur isotopes in the middle Gaoyuzhuang Formation were studied in two sections of the North China Platform. The results show a positive shift in authigenic Cr isotope from −0.18‰ to +0.66‰, which was followed by a decline to −0.16‰. This suggests a rise in atmospheric oxygen sufficient to initiate oxic Cr cycling and isotope fractionation (pO2 > 0.1%–1% PAL). This positive Cr isotope excursion was associated with a transient positive shift in δ34SCAS from ~20‰ to ~50‰ and a subsequent decline to ~10‰, which provides independent evidence of atmospheric oxygenation. This oxygenation may have enhanced oxidative terrestrial weathering and increased sulfate input to the ocean, thus stimulating bacterial sulfate reduction and pyrite burial in deep anoxic seawaters. This is broadly consistent with previous results of carbonate I/(Ca + Mg) and Ce anomaly but also reveals a lag between shallow seawater and atmospheric oxygenation. Fluctuated redox conditions and decoupled oxygenation between shallow seawater and atmosphere during the mid-Proterozoic may help to account for the current debate.
Supplemental Material: Preserved intercratonic lithosphere reveals Proterozoic assembly of Australia
Authors: Lu Yongjun , al. et
Published: July 2022

Detailed descriptions of methods and sample results, Figures S1–S3, and Tables S1 and S2. 
Correct Solvability of Integrodifferential Equations in Spaces of Vector Functions Holomorphic in an Angular Domain
Authors: Vlasov V. V. , Rautian N. A.
Published: July 2022

Integrodifferential equations with unbounded operator coefficients in a Hilbert space are studied. The main part of an equation of this kind is an abstract parabolic equation perturbed by a Volterra integral operator. The fundamental difference between this work and the other ones is that integrodifferential equations are considered and studied in this paper for vector functions the arguments of which take values in an angular domain on the complex plane.
Behavior of Binomial Distribution near Its Median
Authors: Volkov N. A. , Dmitriev D. I. , Zhukovskii M. E.
Published: July 2022

We study the behavior of the cumulative distribution function of a binomial random variable with parameters n and $$b{\text{/}}(n + c)$$ at the point b – 1 for positive integers $$b \leqslant n$$ and real $$c \in [0,\;1]$$. Our results can be applied directly to the well-known problem about small deviations of sums of independents random variables from their expectations. Moreover, we answer the question about the monotonicity of the Ramanujan function for the binomial distribution posed by Jogdeo and Samuels in 1968.
Non-diabetic euglycaemic ketoacidosis and rapid weight loss in a post-traumatic surgical patient: is the outré preventable?
Authors: Chin Yun Xin , Loganathan Nivan , Kirthinanda Dinoo Suran
Published: July 2022

To highlight the implications of the metabolic stress response and the role of anaesthesia in attenuating its deleterious effects, we present this extremely rare case of non-diabetic euglycaemic ketoacidosis with rapid weight loss in a post-traumatic surgical patient. Ketoacidosis is the accumulation of ketone bodies in blood and is generally associated with relative or absolute insulin deficiency secondary to diabetes mellitus, sodium–glucose cotransporter 2 inhibitors and extensive fasting. The stress of systemic disease, trauma or surgery in such predisposed patients could precipitate ketoacidosis. Our patient developed high anion gap metabolic acidosis intraoperatively due to ketosis, a potentially life-threatening complication, without any predisposing factors as a result of metabolic stress of major trauma and surgery. Aiding the interpretation, he lost 15 kg weight perioperatively, suggesting his body was in a hypercatabolic state. This report emphasises the value of anaesthetic techniques to prevent such rare complications.
Pathological complete response to immune checkpoint inhibitor in patients with colorectal cancer liver metastases harboringPOLEexonuclease domain mutation
Authors: Wen Lei , Chen Zhigang , Ji Xiaomeng , Fong William Pat , Shao Qiong , Ren Chao , Cai Yanyu , Li Binkui , Yuan Yunfei , Wang Deshen , Li Yuhong
Published: July 2022

Patients with polymerase epsilon (POLE) exonuclease domain mutation (EDM) exhibits distinct clinical characteristics and extremely high tumor mutation burden (TMB). There is a paucity of data on the therapeutic efficacy of immune checkpoint inhibitors (ICIs) for the treatment of colorectal cancer liver metastases (CRLM) patients withPOLEEDM. Clinical characteristics, radiological and pathological response, as well as oncological outcomes of four CRLM patients harboringPOLEEDM and treated by ICI plus chemotherapy were retrospectively collected and analyzed. TMB and genomic mutation profiling were also assessed in resected CRLM patients harboring different molecular characteristics. The four CRLM patients received toripalimab or sintilimab plus chemotherapy (FOLFOX or FOLFIRI or XELOX) with or without bevacizumab afterPOLEEDM were detected. All four patients achieved a radiological partial response. Staged or simultaneous complete surgical resection of the primary tumor and liver metastases was conducted. Pathological complete response was achieved in all four patients. After a median follow-up of 14 (range 9–20) months, all four patients maintained non-evidence of disease status until the last follow-up.POLEEDM patients showed a larger set of mutational genes compared with non-POLEEDM patients. TMB of patients harboringPOLEEDM was significantly higher than those with microsatellite instability-high (median, 313.92 vs 42.24 mutations/Mb, p<0.05),POLEnon-EDM (313.92 vs 4.80, p<0.001), and MSS subtypes (313.92 vs 4.80, p<0.001). Despite being a rare phenotype, CRLM patients withPOLEEDM exhibit ultra-high TMB and, more importantly, significant clinical response to ICI-based combination therapy. Therefore, the complete sequencing ofPOLEexonuclease domains is recommended in CRLM patients clinically.
Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature
Authors: Wong-Rolle Abigail , Dong Qiang , Zhu Yunhua , Divakar Prajan , Hor Jyh Liang , Kedei Noemi , Wong Madeline , Tillo Desiree , Conner Elizabeth A , Rajan Arun , Schrump David S , Jin Chengcheng , Germain Ronald N , Zhao Chen
Published: July 2022

Background

The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors are missing, information needed for improved prognosis and treatment.

Methods

To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and 3 microbe targets (bacteria, fungi, and cytomegalovirus). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in surgically resected tumor samples from 12 patients with early-stage lung cancer.

Results

Bacterial burden was significantly higher in tumor cells compared with T cells, macrophages, other immune cells, and stroma. This burden increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that lung intratumor bacteria derive from the latter route of entry. Expression of oncogenic β-catenin was strongly correlated with bacterial burden, as were tumor histological subtypes and environmental factors.

Conclusions

Intratumor bacteria were enriched with tumor cells and associated with multiple oncogenic pathways, supporting a rationale for reducing the local intratumor microbiome in lung cancer for patient benefit.

Trial registration number

NCT00242723,NCT02146170.
Baseline and post-treatment biomarkers of resistance to anti-PD-1 therapy in acral and mucosal melanoma: an observational study
Authors: Shui Irene M. , Liu Xiao Qiao , Zhao Qing , Kim Seung Tae , Sun Yuan , Yearley Jennifer H. , Choudhury Tasmiah , Webber Andrea L. , Krepler Clemens , Cristescu Razvan , Lee Jeeyun
Published: July 2022

Background

Immunotherapies targeting programmed cell death-1 (PD-1) and its ligands have improved clinical outcomes for advanced melanoma. However, many tumors exhibit primary resistance or acquire secondary resistance after an initial positive response. The mechanisms of resistance are not well understood, and no validated predictive biomarkers are available. This exploratory study aimed to characterize baseline differences and molecular changes arising during treatment in acral and mucosal melanomas that exhibited primary or secondary resistance to anti-PD-1 monotherapy.

Methods

This was an observational retrospective study of 124 patients who had been treated for metastatic acral or mucosal melanoma with anti-PD-1 monotherapy. Tumor samples were collected at baseline (all patients) and post-treatment (resistant tumors only) and were assayed by immunohistochemistry, whole-exome sequencing, and RNA sequencing.

Results

At baseline, more non-progressor than resistant tumors exhibited expression of PD-L1, immune cell infiltration, and high tumor mutational burden (TMB); baseline PD-L1 expression was also more common in secondary-resistant than in primary-resistant tumors as well as in late versus early secondary-resistant tumors. Non-progressor tumors also had higher median baseline expression of an 18-gene T cell-inflamed gene expression profile (TcellinfGEP). Among resistant tumors, the proportion of PD-L1-positive melanomas and the expression of the TcellinfGEP mRNA signature increased during treatment, while the expression of mRNA signatures related to WNT and INFA1 signaling decreased. There was evidence for greater changes from baseline in secondary-resistant versus primary-resistant tumors for some markers, including expression of RAS-related and WNT-related mRNA signatures and density of CD11c+and FOXP3+T cells. Greater changes in CD11c+cell density were observed in early compared with late secondary-resistant tumors.

Conclusions

Our findings suggest that TcellinfGEP and PD-L1 expression, TMB, immune cell infiltration, and RAS and WNT signaling warrant further investigation as potential mechanisms and/or biomarkers of anti-PD-1 therapy resistance in acral and mucosal melanomas. Confirmation of these findings in larger populations is needed.
Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Authors: Henick Brian S , Villarroel-Espindola Franz , Datar Ila , Sanmamed Miguel F , Yu Jovian , Desai Shruti , Li Alice , Aguirre-Ducler Adam , Syrigos Konstantinos , Rimm David L , Chen Lieping , Herbst Roy S , Schalper Kurt A
Published: July 2022

Background

Despite the prominent role of innate immunity in the antitumor response, little is known about the myeloid composition of human non-small cell lung cancer (NSCLC) with respect to histology and molecular subtype. We used multiplexed quantitative immunofluorescence (QIF) to measure the distribution and clinical significance of major myeloid cell subsets in large retrospective NSCLC collections.

Methods

We established a QIF panel to map major myeloid cell subsets in fixed human NSCLC including 4’,6-Diamidino-2-Phenylindole for all cells, pancytokeratin for tumor-epithelial cells, CD68 for M1-like macrophages; and CD11b plus HLA-DR to interrogate mature and immature myeloid cell populations such as myeloid derived suppressor cells (MDSCs). We interrogated 793 NSCLCs represented in four tissue microarray-based cohorts: #1 (Yale, n=379) and #2 (Greece, n=230) with diverse NSCLC subtypes; #3 (Yale, n=138) with molecularly annotated lung adenocarcinomas (ADC); and #4 (Yale, n=46) with patient-matched NSCLC and morphologically-normal lung tissue. We examined associations between marker levels, myeloid cell profiles, clinicopathologic/molecular variables and survival.

Results

The levels of CD68+ M1 like macrophages were significantly lower and the fraction of CD11b+/HLA-DR− MDSC-like cells was prominently higher in tumor than in matched non-tumor lung tissues. HLA-DR was consistently higher in myeloid cells from tumors with elevated CD68 expression. Stromal CD11b was significantly higher in squamous cell carcinomas (SCC) than in ADC across the cohorts and EGFR-mutated lung ADCs displayed lower CD11b levels than KRAS-mutant tumors. Increased stromal CD68- and HLA-DR-expressing cells was associated with better survival in ADCs from two independent NSCLC cohorts. In SCC, increased stromal CD11b or HLA-DR expression was associated with a trend towards shorter 5-year survival.

Conclusions

NSCLCs display an unfavorable myeloid immune contexture relative to non-tumor lung and exhibit distinct myeloid-cell profiles across histologies and presence of major oncogenic driver-mutations. Elevated M1-like stromal proinflammatory myeloid cells are prognostic in lung ADC, but not in SCC.
Rethinking the immunotherapy numbers game
Authors: Bekker Rebecca A , Zahid Mohammad U , Binning Jennifer M , Spring Bryan Q , Hwu Patrick , Pilon-Thomas Shari , Enderling Heiko
Published: July 2022

Immunotherapies are a major breakthrough in oncology, yielding unprecedented response rates for some cancers. Especially in combination with conventional treatments or targeted agents, immunotherapeutics offer invaluable tools to improve outcomes for many patients. However, why not all patients have a favorable response remains unclear. There is an increasing appreciation of the contributions of the complex tumor microenvironment, and the tumor-immune ecosystem in particular, to treatment outcome. To date, however, there exists no immune biomarker to explain why two patients with similar clinical stage and molecular profile would have different treatment outcomes. We hypothesize that it is critical to understand both the immune and tumor states to understand how the complex system will respond to treatment. Here, we present how integrated mathematical oncology approaches can help conceptualize the effect of various immunotherapies on a patient’s tumor and local immune environment, and how combinations of immunotherapy and cytotoxic therapy may be used to improve tumor response and control and limit toxicity on a per patient basis.
Workforce attachment after a congenital long QT syndrome diagnosis: a Danish nationwide study
Authors: Jespersen Camilla H B , Butt Jawad Haider , Krøll Johanna , Winkel Bo Gregers , Kanters Jørgen K , Gislason Gunnar , Torp-Pedersen Christian , Bundgaard Henning , Jensen Henrik Kjærulf , Køber Lars , Tfelt-Hansen Jacob , Weeke Peter E
Published: July 2022

Objective

To examine workforce attachment among patients with congenital long QT syndrome (cLQTS) following diagnosis and identify factors associated with workforce attachment.

Methods and results

In this nationwide cohort study, all patients diagnosed with cLQTS in Denmark between 1996 and 2016 aged 18–60 years at diagnosis were identified using nationwide registries. Patients attached to the workforce at diagnosis were included. Attachment to the workforce 1 year after cLQTS diagnosis was examined and compared with a background population matched 1:4 on age, sex and employment status. Multiple logistic regression was performed to identify factors associated with 1-year workforce detachment among patients with cLQTS. 298 patients fulfilled the inclusion criteria. Six months after cLQTS diagnosis, 90.9% of patients with cLQTS were attached to the workforce compared with 95.0% in the background population (p=0.006 for difference). One year after diagnosis, 93.3% of patients with cLQTS were attached to the workforce compared with 93.8% in the background population (p=0.26). Among patients with cLQTS, a severe cLQTS disease manifestation was associated with workforce detachment 1 year after diagnosis (compared with asymptomatic patients; aborted cardiac arrest OR 20.4 (95% CI, 1.7 to 249.9); ventricular tachycardia/syncope OR 10.9 (95% CI, 1.1 to 110.5)). No other associated factors were identified.

Conclusions

More than 90% of patients with cLQTS remained attached to the workforce 1 year after diagnosis, which was similar to a matched background population. Patients with a severe cLQTS disease manifestation were less likely to be attached to the workforce 1 year after diagnosis.