bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial drainage‐related prognostic factors for perihilar cholangiocarcinoma: A single‐center retrospective study
Authors: Sato Katsuhiko , Shigekawa Minoru , Kozumi Kazuhiro , Okabe Junya , Sato Yu , Tamura Takeshi , Yoshioka Teppei , Sakamori Ryotaro , Iwagami Yoshifumi , Yamada Daisaku , Tomimaru Yoshito , Noda Takehiro , Takahashi Hidenori , Kobayashi Shogo , Eguchi Hidetoshi , Tatsumi Tomohide , Takehara Tetsuo
Published: May 2022

Objectives

Perihilar cholangiocarcinoma (PCC) is a complex disorder involving the hepatic hilum. Multiple endoscopic retrograde cholangiopancreatography sessions are necessary for diagnosis and treatment with underlying cholangitis risk. Our aim is to clarify the initial‐drainage‐related prognostic factors of PCC.

Methods

This study was a single‐center retrospective study. A total of 104 consecutive patients diagnosed with PCC from January 2010 to February 2020 were enrolled. We defined the diagnostic period as the time between the first biliary drainage attempt and the final drainage when treatment, including surgery or chemotherapy, was started. We focused on this initial period and analyzed the endoscopy‐related factors that affected mortality.

Results

Overall survival of all PCC patients was 599 days. Overall survival of surgically treated patients and unresectable patients were 893 days and 512 days, respectively. In 48 surgically treated patients, drainage‐related cholangitis within the diagnostic period, defined as new cholangitis that occurred after the first biliary drainage attempt, worsened overall survival from 1460 days to 607 days. Endoscopic sphincterotomy, the first drainage method other than endoscopic nasobiliary drainage, and four or more endoscopic retrograde cholangiopancreatography sessions were risk factors for drainage‐related cholangitis. Drainage‐related cholangitis increased pathological lymph node metastasis. Percutaneous transhepatic biliary drainage as final drainage was the only prognostic factor in unresectable chemotherapy‐treated patients.

Conclusions

Drainage‐related cholangitis worsened the prognosis in PCC patients who underwent surgery. Appropriate endoscopic retrograde cholangiopancreatography strategies, especially during the diagnostic period, are of great importance in PCC.
A glimpse on influences of feed additives in aquaculture
Authors: Marimuthu Vignesh , Shanmugam Sureshkumar , Sarawagi Anurag Deendayal , Kumar Abhay , Kim In Ho , Balasubramanian Balamuralikrishnan
Published: May 2022

Aquaculture is one of the most developing sectors worldwide, and it contributes to enhancing the global production. The application of natural feed additives is an external source of aquaculture production due to the ban on antibiotics as a growth promotor as well as their harmful effects on the host, and cost‐effectiveness. Even consumer concerns those antibiotics can cause the water quality and growth instead of growth promoters of natural feed additives to improve the aquaculture production. The role of feed additives is to control the pathogenic microbes, enhance their growth, immune stimulation, and ensure water quality. For these reasons, several types of dietary feed additives are used in the livestock sector, such as essential oil, essential fatty acid, probiotics, prebiotics, symbiotic, and exogenous enzymes, but here, the feed additives of probiotics' most relevant applications in the aquaculture field in terms of modes of action such as strengthening the immune response, competition of binding sites, production of antipathogenic substances, and growth performance competition for nutrition are described. These additives are considered to be useful for their specific medicinal properties and eco‐friendly metabolism in the digestive system. This review describes the role of various feed additives and their relevance to aquaculture production quality.
Prognostic impact of the updated 2018 HFA‐ESC definition of advanced heart failure: results from the HELP‐HF registry
Authors: Pagnesi Matteo , Lombardi Carlo Mario , Chiarito Mauro , Stolfo Davide , Baldetti Luca , Loiacono Ferdinando , Tedino Chiara , Arrigoni Luca , Ghiraldin Daniele , Tomasoni Daniela , Inciardi Riccardo Maria , Maccallini Marta , Villaschi Alessandro , Gasparini Gaia , Montella Marco , Contessi Stefano , Cocianni Daniele , Perotto Maria , Barone Giuseppe , Merlo Marco , Cappelletti Alberto Maria , Sinagra Gianfranco , Pini Daniela , Metra Marco
Published: May 2022

Aims

The Heart Failure Association of the European Society of Cardiology (HFA‐ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high‐risk HF.

Methods and results

The HELP‐HF registry enrolled consecutive patients with HF and at least one high‐risk ‘I NEED HELP’ marker, evaluated at four Italian centres between 1st January 2020 and 30th November 2021. Patients meeting the HFA‐ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all‐cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high‐risk ‘I NEED HELP’ marker were included (mean age 75.1 ± 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%–50%]). Among them, 193 (16.8%) patients met the HFA‐ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1‐year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA‐ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82–2.74, p < 0.001). The prognostic impact of the HFA‐ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57–2.50, p < 0.001).

Conclusions

The HFA‐ESC advanced HF definition had a strong prognostic impact in a contemporary, real‐world, multicentre high‐risk cohort of patients with HF.
Synergistic Dual Amine/Transition Metal Catalysis: Recent Advances
Authors: Venugopalan Nair Vysakh , Arunprasath Dhanarajan , Pandidurai Solai , Sekar Govindasamy
Published: May 2022

Dual Catalysis has enabled a plethora of novel unconventional transformations that would have been unattainable by either catalyst alone. The enormous potential of dual catalysis hinges on the synergistic activation of two substrates in discrete catalytic cycles without interfering with one another. The last decade had witnessed diverse dual‐catalyst systems focusing mainly on the combination of transition metal catalysis with either one of Lewis acid catalysis, photoredox catalysis, biocatalysis or organocatalysis (i. e., Lewis bases, Brønsted acids and NHC catalysts). In this setting, the scientific community has greatly embraced the integration of amine catalysts with transition metal catalysts. This Review comprehends the reported examples from the past decade on dual amine/transition metal catalysis and discuss the various activation modes for the functionalisation of carbonyl compounds.
Altered prefrontal‐striatal theta‐band oscillatory dynamics underlie working memory deficits in neuropathic pain rats
Authors: Cardoso‐Cruz Helder , Laranjeira Inês , Monteiro Clara , Galhardo Vasco
Published: May 2022

Background

Prelimbic medial prefrontal cortex (PL‐mPFC) and nucleus accumbens core region (NAcc) play an important role in supporting several executive cognitive mechanisms, such as spatial working memory (WM). Recently, this circuit has been also associated with both sensory and affective components of pain. However, it is still unclear whether this circuit is endogenously engaged in neuropathic pain‐related cognitive dysfunctions.

Methods

To answer this question, we induced the expression of halorhodopsin in local PL‐mPFC neurons projecting to NAcc, and then selectively inhibited the terminals of these neurons in the NAcc while recording neural activity during the performance of a delayed non‐match to sample (DNMS) spatial WM task. Within‐subject behavioural performance and PL‐mPFC to NAcc circuit neural activity was assessed after the onset of a persistent rodent neuropathic pain model—spared nerve injury (SNI).

Results

Our results revealed that the induction of the neuropathy reduced WM performance, and altered the interplay between PL‐mPFC and NAcc neurons namely in increasing the functional connectivity from NAcc to PL‐mPFC, particularly in the theta‐band spontaneous oscillations; in addition, these behavioural and functional perturbations were partially reversed by selective optogenetic inhibition of PL‐mPFC neuron terminals into the NAcc during the DNMS task delay‐period, without significant antinociceptive effects.

Conclusions

Altogether, these results strongly suggest that the PL‐mPFC excitatory output into the NAcc plays an important role in the deregulation of WM under pain conditions.

Significance

Selective optogenetic inhibition of prefrontal‐striatal microcircuit reverses pain‐related working memory deficits but has no significant impact on pain responses. Neuropathic pain underlies an increase of functional connectivity between the nucleus accumbens core area and the prelimbic medial prefrontal cortex mediated by theta‐band activity.
Novel synthetic co‐culture of Acetobacterium woodii and Clostridium drakei using CO2 and in situ generated H2 for the production of caproic acid via lactic acid
Authors: Herzog Jan , Mook Alexander , Guhl Lotta , Bäumler Miriam , Beck Matthias H. , Weuster‐Botz Dirk , Bengelsdorf Frank R. , Zeng An‐Ping
Published: May 2022

Acetobacterium woodii is known to produce mainly acetate from CO2 and H2, but the production of higher value chemicals is desired for the bioeconomy. Using chain‐elongating bacteria, synthetic co‐cultures have the potential to produce longer‐chained products such as caproic acid. In this study, we present first results for a successful autotrophic co‐cultivation of A. woodii mutants and a Clostridium drakei wild‐type strain in a stirred‐tank bioreactor for the production of caproic acid from CO2 and H2 via the intermediate lactic acid. For autotrophic lactate production, a recombinant A. woodii strain with a deleted Lct‐dehydrogenase complex, which is encoded by the lctBCD genes, and an inserted D‐lactate dehydrogenase (LdhD) originating from Leuconostoc mesenteroides, was used. Hydrogen for the process was supplied using an All‐in‐One electrode for in situ water electrolysis. Lactate concentrations as high as 0.5 g L–1 were achieved with the AiO‐electrode, whereas 8.1 g L–1 lactate were produced with direct H2 sparging in a stirred‐tank bioreactor. Hydrogen limitation was identified in the AiO process. However, with cathode surface area enlargement or numbering‐up of the electrode and on‐demand hydrogen generation, this process has great potential for a true carbon‐negative production of value chemicals from CO2.
Comments on “Biosorption of nickel from aqueous solution onto Liagora viscida: Kinetics, isotherm, and thermodynamics”
Authors: Tran Hai Nguyen , Bollinger Jean‐Claude , Lima Eder C.
Published: May 2022

In 2020, Komarabathina and colleagues published the paper above (the original paper). They used the Liagora viscida‐based biosorbent for adsorbing nickel ions from water. Kinetics, isotherm, and thermodynamics are three important components for the correct description of an adsorption process. However, the authors of the original paper introduced several fundamental errors in these three parts. Other important problems in the original paper are inconsistencies between the experimental data and their modeling results, as well as errors in units. Therefore, we present detailed analyses of these mistakes, hoping that this “comment” paper will also be useful to other researchers (especially beginners) to avoid finding such mistakes elsewhere in the future.
Partitioned analysis of soil‐structure interaction for Nuclear Island Buildings
Authors: Chen Shaolin , Lv Hao , Zhou Guoliang
Published: May 2022

The present methods for three‐dimensional time‐domain soil‐structure interaction (SSI) analysis are often uneconomical because they are performed with a single time integration scheme and a single time step, which prohibits their application to large‐scale SSI problems. In this study, a partitioned analysis of SSI (PASSI) is proposed for enhancing SSI computational efficiency. This is accomplished by partitioning the soil‐foundation‐structure system into the soil (foundation) and structure subsystems and implementing the continuity conditions of the displacements and reaction forces at the soil (foundation)‐structure interface in a primal way. A lumped‐mass explicit finite element method and a transmitting artificial boundary are used to model the unbounded soil, the structure is analyzed via the implicit finite element method, and the response of the rigid foundation is calculated through an explicit time integration scheme. The solution is separately advanced over time for each subsystem. Different time steps can be chosen for the explicit and implicit integration schemes, which can greatly improve efficiency. Interaction effects are accounted for by the transmission and synchronization of the coupled state variables. In addition, intrafield and interfield parallel procedures for PASSI are developed, and their theoretical efficiencies are analyzed. A simple example is provided to verify the performance of the partitioned approach with an explicit‐implicit co‐computation and to compare it to the fully explicit approach. Finally, the seismic response analysis of a nuclear power plant is presented to validate the feasibility and efficiency of the intrafield and interfield parallel procedures.
Nitrogen‐doped porous nanocarbons‐conducting polymer composite film electrodes for flexible supercapacitors
Authors: Kim Hyunjun , Jung Euiyeon , Shin Joobee , Gu Min Guk , Kim Sung‐Kon
Published: May 2022

Heteroatom‐doped carbtableons derived from carbonization of highly porous metal organic framework (MOF) nanocrystals have received tremendous attention due to their exceptional surface areas. They can be used as conductive supports for various electrocatalysts. Depending on the synthesis, various MOFs with different coordination structures, morphologies, and porosities can be designed for versatile applications such as gas storage, catalysis, and energy storage systems. In this work, we combine nitrogen‐doped carbon nanoparticles derived from zeolitic imidazolate framework (ZIF‐8) with PEDOT:PSS, a conductive polymer mixture, for highly flexible supercapacitor electrode. The composite film exhibits a 3D interconnected network favorable for fast charge transfer kinetics with a high surface area. This nitrogen‐doped porous carbon‐PEDOT:PSS composite film shows good specific energy of 7.19 Wh kg−1 and good rate performance as well as long cycle life for at least 5000 charge‐discharge cycles.
Recent applications of immunomodulatory biomaterials for disease immunotherapy
Authors: Dai Huaxing , Fan Qin , Wang Chao
Published: May 2022

Immunotherapy is used to regulate systemic hyperactivation or hypoactivation to treat various diseases. Biomaterial‐based immunotherapy systems can improve therapeutic effects through targeted drug delivery, immunoengineering, etc. However, the immunomodulatory effects of biomaterials themselves cannot be neglected. In this review, we outline biomaterials with immunomodulatory functions discovered in recent years and their applications in disease treatment. These biomaterials can treat inflammation, tumors, or autoimmune diseases by regulating immune cell function, exerting enzyme‐like activity, neutralizing cytokines, etc. The prospects and challenges of biomaterial‐based modulation of immunotherapy are also discussed.
Lipoxygenase‐catalysed co‐oxidation for sustained production of oxyfunctionalized terpenoids
Authors: Nikolaiczyk Vanessa , Kirschning Andreas , Díaz Edison
Published: May 2022

Lipoxygenases (LOX) catalyse allylic oxidations and epoxidations of a co‐substrate in the presence of an unsaturated fatty acid containing a 1,4‐pentadiene moiety. One‐ and two‐step enzyme assays were established to verify the role or involvement of LOX in such co‐oxidations. It was shown that LOX is only involved in the formation of reactive hydroperoxides, but not in the oxidation of a co‐substrate, assuming a mechanism involving free peroxy radicals for the latter. Ten mono‐ and sesquiterpenes were used as co‐substrates and the resulting products were analysed by mass spectrometry. A semi‐preparative approach was developed using (+)‐valencene as an example, and the resulting products were isolated by preparative GC and their structures elucidated by NMR spectroscopy.
Modeling and monitoring submerged prehistoric sites during offshore sand dredging and implications for the study of Early Holocene Coastal Occupation of Southern California
Authors: Hildebrand John A. , York Andrew L.
Published: May 2022

Beach sand dredging projects off the coast of Southern California provide data for improved understanding of the stratigraphic setting for early Holocene sediments and the potential for offshore buried archaeological materials. Geophysical data, core sediments, and invertebrate fossils allow models to be developed for six borrow sites within drown river valleys off San Diego County. These site‐specific models were tested during dredging operations, and the dredge spoil was monitored for archaeological materials. Two of the borrow sites yielded stone bowls consistent with those found in previous offshore archaeological investigations in this region. These artifacts, however, were determined to come from nearshore and lagoonal sediments, not appropriate for direct occupation, raising questions about both the function of stone bowls and the process that resulted in their deposition. The competing hypotheses presented are that these bowls originated in settlements located adjacent to the lagoons, but were eroded and redeposited into the lagoon during transgression, or that they were part of a fishing toolkit used from boats or in shallow waters within the lagoon. This project illustrates the potential for commercial development projects to yield information on submerged archaeological resources, as well as the challenges.
Genesis of the late‐stage base metal sulfide mineralisation and its relationship with the regional deformation in Ambaji–Deri, South Delhi Terrane, North‐West India
Authors: Sharma Neeraj Kumar , Chinnasamy Sakthi Saravanan , Biswal Tapas Kumar
Published: May 2022

Proterozoic stratiform VMS‐type Ambaji–Deri Zn–Pb–Cu deposits in the Aravalli‐Delhi mobile belt of North‐West India are hosted within meta‐sedimentary sequences of the South Delhi Terrane. Several fracture‐filled discordant late‐stage base metal mineralised quartz veins have intruded along with the fractures and foliation at very high Pf (σ2 < Pf < σ1) with typical hydrothermal alteration zones. Temperatures estimated from hydrothermal chlorite vary from 226 to 293°C (mean. 260°C). 40Ar‐39Ar dating of hydrothermal muscovite yielded a plateau age of 625.5 ± 3.3 Ma. Detailed fluid inclusion (FI) analysis reveals three types of primary and four types of secondary FI. Primary H2O‐NaCl‐CO2 ± N2 type 1a FI has medium to high salinity (11.21–21.96 wt% NaCl equivalent) and high density (0.90–1.04 g/cm3), while the secondary type 1b FI with same compositions are characterized by medium salinity (~12.6 wt% NaCl equivalent) and lower density (0.89–0.90 g/cm3). Phase separation/fluid immiscibility is the primary mechanism of mineralisation in the Ambaji–Deri that caused the original fluid to evolve separately as gaseous (CO2) type 2a, b and aqueous type 3a, b (H2O‐NaCl) with similar salinity and density for the aqueous inclusions and low density for the gaseous inclusions (lowering up to 0.58 g/cm3). The ore‐forming fluid with magmatic signatures possibly originated from the cooling G3 granites, remobilized the pre‐existing metals, and precipitated at ~265°C and ~1 kbar at the epizonal depths in the dilated fractures. Later these fluids are mixed with meteoric water and evolved into low saline aqueous fluids that produced supergene alterations.
Age‐related topographic map of magnetic resonance diffusion metrics in neonatal brains
Authors: Bobba Pratheek S. , Weber Clara F. , Mak Adrian , Mozayan Ali , Malhotra Ajay , Sheth Kevin N. , Taylor Sarah N. , Vossough Arastoo , Grant Patricia Ellen , Scheinost Dustin , Constable Robert Todd , Ment Laura R. , Payabvash Seyedmehdi
Published: May 2022

Accelerated maturation of brain parenchyma close to term‐equivalent age leads to rapid changes in diffusion‐weighted imaging (DWI) and diffusion tensor imaging (DTI) metrics of neonatal brains, which can complicate the evaluation and interpretation of these scans. In this study, we characterized the topography of age‐related evolution of diffusion metrics in neonatal brains. We included 565 neonates who had MRI between 0 and 3 months of age, with no structural or signal abnormality—including 162 who had DTI scans. We analyzed the age‐related changes of apparent diffusion coefficient (ADC) values throughout brain and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) along white matter (WM) tracts. Rate of change in ADC, FA, and MD values across 5 mm cubic voxels was calculated. There was significant reduction of ADC and MD values and increase of FA with increasing gestational age (GA) throughout neonates' brain, with the highest temporal rates in subcortical WM, corticospinal tract, cerebellar WM, and vermis. GA at birth had significant effect on ADC values in convexity cortex and corpus callosum as well as FA/MD values in corpus callosum, after correcting for GA at scan. We developed online interactive atlases depicting age‐specific normative values of ADC (ages 34–46 weeks), and FA/MD (35–41 weeks). Our results show a rapid decrease in diffusivity metrics of cerebral/cerebellar WM and vermis in the first few weeks of neonatal age, likely attributable to myelination. In addition, prematurity and low GA at birth may result in lasting delay in corpus callosum myelination and cerebral cortex cellularity.
Hematologic malignancies and COVID‐19 infection: A monocenter retrospective study
Authors: Azhdari Tehrani Hamed , Ramezaninejad Soodeh , Mardani Masoud , Shokouhi Shervin , Darnahal Maryam , Hakamifard Atousa
Published: May 2022

Introduction

Hematologic malignancies are risk factors for severe COVID‐19 infection. Identification of risk factors correlated with mortality in these groups of patients is important in the assessment strategy. We studied the characteristics of patients with hematologic malignancies and COVID‐19 and then analyzed the predictors of mortality.

Methods

Eligible for the analysis were hospitalized patients with hematologic malignancies and confirmed COVID‐19 infection observed between January 2020 and March 2021. Patients were categorized based on the type of malignancy and phase of the treatment.

Results

A total of 194 COVID‐19 infected patients with hematologic malignancies were included. The median age was 44 (15–81) years; 135 of them were males and 59 were females. Acute myeloid leukemia was the most frequent cancer type (43.8%). A total of 119 patients had severe COVID‐19 and 61 patients were admitted to the intensive care unit. A total of 92 deaths occurred in all cases for an overall case‐fatality rate of 47%. Male gender, preinduction and induction phase of the treatment, intensive care admission, low levels of oxygen saturation, Rhesus (RH) factor positivity, and higher fibrinogen level correlated with mortality.

Conclusion

This study focuses on the epidemiology, risk factors, outcomes, and predictors of mortality of COVID‐19 among patients with hematologic malignancies. Patients with hematologic malignancies are at high risk of mortality.
Association of ABO blood group with in‐hospital adverse outcome and long term persistent symptoms of COVID‐19 infection: A single‐center longitudinal observational study
Authors: Nafakhi Ahmed , Rabeea Ihsan S. , Al‐Darraji Rasha , Nafakhi Hussein , Mechi Ahmed , Al‐Khalidi Alhan , alareedh Mohammed
Published: May 2022

Background and Aims

There are gaps in knowledge regarding the association between the ABO blood group and coronavirus disease 2019 (COVID‐19) immediate and long‐term outcomes. We aimed to investigate the association of ABO blood group with COVID‐19 in‐hospital adverse outcomes and to determine whether ABO blood group is associated with post‐COVID‐19 persistent symptoms.

Methods

This was a single‐center longitudinal observational study that included patients who presented with symptoms suggestive of COVID‐19 infection and a positive test for COVID‐19 and were able to attend the out‐patient clinic after 6 months following acute COVID‐19. The main outcomes were intensive care unit admission, the requirement for respiratory support, in‐hospital death, and persistent symptoms. χ2 test and regression analysis were used to analyze the collected data.

Results

A total of 169 patients were enrolled for the assessment of in‐hospital adverse outcomes of whom 86 patients were included for the assessment of persistent symptoms after the exclusion of deceased patients or patients not attended the out‐patient clinic. Patients with blood group B had higher prevalence of in‐hospital death compared to blood group O (39% vs. 13%, p = 0.01) and this persisted after adjusting for sex (odds ratio, OR [confidence interval, CI] = 1.4 [1.1–2.1], p = 0.04), while patients with blood group AB had higher prevalence of requiring respiratory support than blood group O (54% vs. 10%, p = 0.02) and this persisted after adjusting for age (OR [CI] = 1.5 [1.1–2.3], p = 0.02). Concerning the association of ABO blood group and long‐term symptoms, blood group AB showed a higher prevalence of palpitation (p < 0.001) and dizziness (p = 0.02) than other blood groups.

Conclusions

Blood groups AB and B are significantly associated with respiratory support use and in‐hospital death, respectively, compared to blood group O. Blood group AB is significantly associated with persistent palpitation and dizziness compared to other blood groups.
Survival after neoadjuvant/induction combination immunotherapy vs combination platinum‐based chemotherapy for locally advanced (Stage III) urothelial cancer
Authors: Einerhand Sarah M. H. , van Dijk Nick , van Dorp Jeroen , de Feijter Jeantine M. , van Montfoort Maurits L. , van de Kamp Maaike W. , Schaake Eva E. , Boellaard Thierry N. , Hendricksen Kees , van der Heijden Michiel S. , van Rhijn Bas W. G.
Published: May 2022

Despite treatment with cisplatin‐based chemotherapy and surgical resection, clinical outcomes of patients with locally advanced urothelial carcinoma (UC) remain poor. We compared neoadjuvant/induction platinum‐based combination chemotherapy (NAIC) with combination immune checkpoint inhibition (cICI). We identified 602 patients who attended our outpatient bladder cancer clinic in 2018 to 2019. Patients were included if they received NAIC or cICI for cT3‐4aN0M0 or cT1‐4aN1‐3M0 UC. NAIC consisted of cisplatin‐based chemotherapy or gemcitabine‐carboplatin in case of cisplatin‐ineligibility. A subset of patients (cisplatin‐ineligibility or refusal of NAIC) received ipilimumab plus nivolumab in the NABUCCO‐trial (NCT03387761). Treatments were compared using the log‐rank test and propensity score‐weighted Cox regression models. We included 107 Stage III UC patients treated with NAIC (n = 83) or cICI (n = 24). NAIC was discontinued in 11 patients due to progression (n = 6; 7%) or toxicity (n = 5; 6%), while cICI was discontinued in 6 patients (25%) after 2 cycles due to toxicity (P = .205). After NAIC, patients had surgical resection (n = 50; 60%), chemoradiation (n = 26; 30%), or no consolidating treatment due to progression (n = 5; 6%) or toxicity (n = 2; 2%). After cICI, all patients underwent resection. After resection (n = 74), complete pathological response (ypT0N0) was achieved in 11 (22%) NAIC‐patients and 11 (46%) cICI‐patients (P = .056). Median (IQR) follow‐up was 26 (20‐32) months. cICI was associated with superior progression‐free survival (P = .003) and overall survival (P = .003) compared to NAIC. Our study showed superior survival in Stage III UC patients pretreated with cICI if compared to NAIC. Our findings provide a strong rationale for validation of cICI for locally advanced UC in a comparative phase‐3 trial.
Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas
Authors: von Knebel Doeberitz Nikolaus , Paech Daniel , Sturm Dominik , Pusch Stefan , Turcan Sevin , Saunthararajah Yogen
Published: May 2022

Glial‐lineage malignancies (gliomas) recurrently mutate and/or delete the master regulators of apoptosis p53 and/or p16/CDKN2A, undermining apoptosis‐intending (cytotoxic) treatments. By contrast to disrupted p53/p16, glioma cells are live‐wired with the master transcription factor circuits that specify and drive glial lineage fates: these transcription factors activate early‐glial and replication programs as expected, but fail in their other usual function of forcing onward glial lineage‐maturation—late‐glial genes have constitutively “closed” chromatin requiring chromatin‐remodeling for activation—glioma‐genesis disrupts several epigenetic components needed to perform this work, and simultaneously amplifies repressing epigenetic machinery instead. Pharmacologic inhibition of repressing epigenetic enzymes thus allows activation of late‐glial genes and terminates glioma self‐replication (self‐replication = replication without lineage‐maturation), independent of p53/p16/apoptosis. Lineage‐specifying master transcription factors therefore contrast with p53/p16 in being enriched in self‐replicating glioma cells, reveal a cause‐effect relationship between aberrant epigenetic repression of late‐lineage programs and malignant self‐replication, and point to specific epigenetic targets for noncytotoxic glioma‐therapy.
Multispectral retinal video‐ophthalmoscope with fiber optic illumination
Authors: Kolar Radim , Vicar Tomas , Odstrcilik Jan , Valterova Eva , Skorkovska Karolina , Kralik Martin , Tornow Ralf‐Peter
Published: May 2022

Multispectral imaging is used in various applications including astronomy, industry and agriculture. In retinal imaging, the single‐shot multispectral image stack is typically acquired and analyzed. This multispectral analysis can provide information on various structural or metabolic properties. This paper describes the multispectral improvement of a video‐ophthalmoscope, which can acquire retinal video sequences of the optic nerve head and peripapillary area using various spectral light illumination. The description of the multispectral video imaging is provided and several applications are described. These applications include multispectral retinal photoplethysmography, visualization of spontaneous vein pulsation and multispectral RGB image generation.
Specific bio‐functionalCBD‐PR1Ppeptide bindingVEGFto collagen hydrogels promotes the recovery of cerebral ischemia in rats
Authors: Yin Jia , Shi Chunying , He Wenli , Yan Wenjing , Deng Jin , Zhang Bing , Yin Mengmeng , Pei Haitao , Wang Haiping
Published: May 2022

Ischemic stroke was a leading cause of death and long‐term disability. It was an effective way to improve cerebral ischemia injury by promoting angiogenesis and neuroprotection. Vascular endothelial growth factor (VEGF) was a potent pro‐angiogenic factor, and had neuroprotective effect. A short peptide (PR1P) derived from the extracellular VEGF‐binding glycoprotein‐Prominin‐1 was reported to specifically bind to VEGF. In order to realize sustained release of VEGF, a bio‐functional peptide‐CBD‐PR1P was constructed, which target VEGF to collagen hydrogels to limit the diffusion of VEGF. When the collagen hydrogels loading with CBD‐PR1P and VEGF were injected into the cerebral ischemic cortex, increased angiogenesis, decreased apoptosis and enhanced neurons survival were observed in the ischemic area, that promoted the motor functional recovery of cerebral ischemic injury. Thus, this targeting delivery system of VEGF provided a promising therapeutic strategy for cerebral ischemia.
Pregnancy Vitamin D Supplementation and Childhood Bone Mass at Age 4 Years: Findings From the Maternal Vitamin D Osteoporosis Study (MAVIDOS) Randomized Controlled Trial
Authors: Curtis Elizabeth M. , Moon Rebecca J. , D'Angelo Stefania , Crozier Sarah R. , Bishop Nicholas J. , Gopal‐Kothandapani Jaya Sujatha , Kennedy Stephen H. , Papageorghiou Aris T. , Fraser Robert , Gandhi Saurabh V. , Schoenmakers Inez , Prentice Ann , Inskip Hazel M. , Godfrey Keith M. , Javaid M. Kassim , Eastell Richard , Cooper Cyrus , Harvey Nicholas C. ,   the MAVIDOS Trial Group
Published: May 2022

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter‐born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long‐term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single‐center follow‐up of a double‐blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25‐hydroxyvitamin D level 25–100 nmol/L from three research centers (2008–2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013–2018). Anthropometry and dual‐energy X‐ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4‐year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472–0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466–0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age‐ and sex‐adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal‐child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Distinct patterns of gene expression during regeneration and asexual reproduction in the annelid Pristina leidyi
Authors: del Olmo Irene , Verdes Aida , Álvarez‐Campos Patricia
Published: May 2022

Regeneration, the ability to replace lost body parts, is a widespread phenomenon in the animal kingdom often connected to asexual reproduction or fission, since the only difference between the two appears to be the stimulus that triggers them. Both developmental processes have largely been characterized; however, the molecular toolkit and genetic mechanisms underlying these events remain poorly unexplored. Annelids, in particular the oligochaete Pristina leidyi, provide a good model system to investigate these processes as they show diverse ways to regenerate, and can reproduce asexually through fission under laboratory conditions. Here, we used a comparative transcriptomics approach based on RNA‐sequencing and differential gene expression analyses to understand the molecular mechanisms involved in anterior regeneration and asexual reproduction. We found 291 genes upregulated during anterior regeneration, including several regeneration‐related genes previously reported in other annelids such as frizzled, paics, and vdra. On the other hand, during asexual reproduction, 130 genes were found upregulated, and unexpectedly, many of them were related to germline development during sexual reproduction. We also found important differences between anterior regeneration and asexual reproduction, with the latter showing a gene expression profile more similar to that of control individuals. Nevertheless, we identified 35 genes that were upregulated in both conditions, many of them related to cell pluripotency, stem cells, and cell proliferation. Overall, our results shed light on the molecular mechanisms that control anterior regeneration and asexual reproduction in annelids and reveal similarities with other animals, suggesting that the genetic machinery controlling these processes is conserved across metazoans.
Domestication and the comparative embryology of birds
Authors: Cordero Gerardo A. , Werneburg Ingmar
Published: May 2022

Studies of domesticated animals have greatly contributed to our understanding of avian embryology. Foundational questions in developmental biology were motivated by Aristotle's observations of chicken embryos. By the 19th century, the chicken embryo was at the center stage of developmental biology, but how closely does this model species mirror the ample taxonomic diversity that characterizes the avian tree of life? Here, we provide a brief overview of the taxonomic breadth of comparative embryological studies in birds. We particularly focused on staging tables and papers that attempted to document the timing of developmental transformations. We show that most of the current knowledge of avian embryology is based on Galliformes (chicken and quail) and Anseriformes (duck and goose). Nonetheless, data are available for some ecologically diverse avian subclades, including Struthioniformes (e.g., ostrich, emu) and Sphenisciformes (penguins). Thus far, there has only been a handful of descriptive embryological studies in the most speciose subclade of Aves, that is, the songbirds (Passeriniformes). Furthermore, we found that temporal variances for developmental events are generally uniform across a consensus chronological sequence for birds. Based on the available data, developmental trajectories for chicken and other model species appear to be highly similar. We discuss future avenues of research in comparative avian embryology in light of the currently available wealth of data on domesticated species and beyond.
AlGaN‐based solar‐blind avalanche photodetectors with gradually doped charge layer
Authors: Yao Yufei , Jiang Xuecheng , Gu Yan , Yang Guofeng , Wei Chunlei , Xie Zhijian , Zhang Qi , Qian Weiying , Zhu Chun
Published: May 2022

To improve the performances of AlGaN solar‐blind ultraviolet (UV) avalanche photodetectors (APDs), we propose a separate absorption and multiplication (SAM) AlGaN APD with a gradually doped charge layer. The calculation results indicate that the designed APD can significantly increase the maximum gain by almost 40%, and reduce the breakdown voltage by about 9% compared with the conventional AlGaN APD. The parameters of multiplication layer and p‐type layer are optimized, and the physical mechanism is described in detail, which provides theoretical guidance for high‐performance device structure design and experimental preparation.
The role of land surface schemes in non‐hydrostatic RegCM on the simulation of Indian summer monsoon
Authors: Raju Pemmani Venkata Subba , Karadan Muhammed Muhshif , Prasad Dasari Hari
Published: May 2022

This study evaluates the performance of a non‐hydrostatic Regional Climate Model (RegCM) with two land surface parameterizations, namely Biosphere‐Atmosphere Transfer (BAT) scheme and Community Land Model (CLM) scheme on the simulation of summer monsoon over India. The initial and boundary conditions are taken from ERA‐Interim (ERA‐I) reanalysis available at a 0.75° spatial grid. The RegCM is designed with 25 km horizontal resolution and 23 vertical levels, and it integrated for the period 1st January 1982 to 30th September 2016. We used the NOAA Optimum Interpolation Weekly sea surface temperatures, the topography and land‐use data from the United States Geological Survey, and Global Land Cover Characterization. Our results reveal that the summer monsoon precipitation anomaly is reasonably well simulated with BAT and CLM schemes compared to those of India Meteorological Department (IMD) observations. The spatial distributions of temperature anomaly over India with BAT compared to CRU shows cold bias over most of the Indian sub‐continent, whereas the CLM shows large warm bias over central India and monsoon trough region. The low‐level and upper‐level winds are in good agreement with ERA‐I. Further, the analysis of extreme monsoon events (i.e., excess and deficit seasons) reveals that CLM depicts less bias in simulating the excess and deficit precipitation regions as compared to those of BAT. Conversely, BAT simulates temperature well over India in both excess and deficit monsoon seasons. The Taylor's diagram analysis, Added Value Index based on Mean Square Error, and Modified Brier Skill Score are also applied for the extreme rainfall seasons. Our quantitative analysis demonstrates that the CLM have resolved better rainfall features with more skills with respect to that of BAT. The results suggest that CLM have added value in Indian Summer Monsoon (ISM) regional climate simulation than the BAT, particularly on simulation of the rainfall characteristics during extreme rainfall seasons.
A benchmarking scoping review of research output from hospital pharmacy departments in Australia
Authors: Penm Jonathan , Narayan Sujita , Alffenaar Jan‐Willem , Johnson Jacinta L. , Mirkov Sanja , Page Amy T. , Pont Lisa G. , Patanwala Asad E.
Published: May 2022

Aim

To benchmark annual research output from hospital pharmacy departments in Australian principal referral hospitals.

Data sources

Embase, Medline, and Scopus.

Study selection

All 29 principal referral hospitals listed by the Australian Institute of Health and Welfare were searched using the institution field from 2018–2020. Articles were included if an author was affiliated with a hospital pharmacy department. Conference abstracts, letters, narrative reviews, opinions, commentaries, or editorials were excluded.

Results

A total of 261 research articles were identified from 27 principal referral hospital pharmacy departments from 2018–2020. Median research output over 3 years was five (interquartile range, 3–9) articles. In terms of annual research, hospital pharmacy departments in the 50th and 90th percentile for total publication output published two and ten original research articles every year, respectively. Overall, 56% (n = 145) of the published studies were observational, 35% (n = 90) had a first author with a pharmacy department affiliation, 97% (n = 252) had at least one author with a university affiliation, and in 5% (n = 12) of the articles there was more than one hospital pharmacy department affiliation.

Conclusion

On average, hospital pharmacy departments in Australian principal referral hospitals publish two original research articles every year. Nearly all of these articles are published in collaborations with universities.
Trends and factors affecting approach choice to pulmonary resection
Authors: Mitzman Brian , Wang Xuechen , Haaland Ben , Varghese Thomas K.
Published: May 2022

Background

The development of an advanced robotic platform in 2014 led to increased adoption of minimally invasive (MI) approaches in thoracic surgery. Due to dataset reporting lag, a comprehensive assessment of trends in thoracic approaches has not been analyzed to date.

Methods

We queried the National Cancer Database (NCDB) for patients with Stage I–III who underwent lung resection from 2010 to 2018. Most published NCDB analyses on lung cancer using pre‐2015 data. Overall treatment trends were analyzed, with geographic, institutional, and socioeconomic characteristics evaluated for approach.

Results

There were 162 335 lung resections, and 131 958 were anatomic. Robotic resection saw a steady increase through 2012 but plateaued in 2013–2014. From 2015 to 2018, another increase correlated with the release of a new platform. Video‐assisted thoracoscopic surgery lung resection plateaued in 2014 and decreased in 2018. Open resection steadily decreased. Tumors requiring neoadjuvant radiation had an increase in MI approach with corresponding decreases in the open. On multivariable analysis, African–American race, low volume, Medicaid insurance, and nonacademic setting were associated with a lower likelihood of MI surgery.

Conclusions

The open approach has decreased since 2010. More than 65% of anatomic resections are now performed in MI. As this trend will continue, it is important that all patients are afforded the opportunity of the least invasive approach.
Water chemistry variation in tropical high‐mountain lakes on old volcanic bedrocks
Authors: Mosquera Pablo V. , Hampel Henrietta , Vázquez Raúl F. , Catalan Jordi
Published: May 2022

Water chemistry and its ecological implications have been extensively investigated in temperate high‐mountain lakes because of their role as sentinels of global change. However, few studies have considered the drivers of water chemistry in tropical mountain lakes underlain by volcanic bedrock. A survey of 165 páramo lakes in the Cajas Massif of the Southern Ecuador Andes identified 4 independent chemical variation gradients, primarily characterized by divalent cations (hardness), organic carbon, silica, and iron levels. Hardness and silica factors showed contrasting relationships with parent rock type and age, vegetation, aquatic ecosystems in the watershed, and lake and watershed size. Geochemical considerations suggest that divalent cations (and related alkalinity, conductivity, and pH) mainly respond to the cumulative partial dissolution of primary aluminosilicates distributed throughout the subsurface of watersheds, and silica and monovalent cations are associated with the congruent dissolution of large amounts of secondary aluminosilicates localized in former hydrothermal or tectonic spots. Dissolved organic carbon was much higher than in temperate high‐mountain lakes, causing extra acidity in water. The smaller the lakes and their watersheds, the higher the likelihood of elevated organic carbon and metals and low hardness. The watershed wetland cover favored metal levels in the lakes but not organic carbon. Phosphorus, positively, and nitrate, negatively, weakly correlated with the metal gradient, indicating common influence by in‐lake processes. Overall, the study revealed that relatively small tropical lake districts on volcanic basins can show chemical variation equivalent to that in large mountain ranges with a combination of plutonic, metamorphic, and carbonate rock areas.
Latest developments in designing advanced lubricants and greases for electric vehicles—An overview
Authors: Shah Raj , Gashi Blerim , Rosenkranz Andreas
Published: May 2022

According to the Environmental Protection Agency, transportation is the largest contributor of greenhouse gas emissions (28% of total emissions). Electric vehicles have remarkably grown in popularity and represent a greener future for the automotive industry. This growth has prompted lubricant and grease technology to adapt to an entirely new environment, which is exposed to new factors including external electric currents/fields and extreme temperatures and pressures originating from electric motors and power electronics. Consequently, novel lubricants and greases need to be developed and explored to ultimately improve fuel efficiency and performance. Nano‐additives have offered exceptional opportunities to enhance electrical, thermal and tribological properties of the lubricants and greases used. It is thus vital to fully explore and understand the effects of nanoparticles' addition to lubricants and greases, as well as the mechanisms by which improvements are obtained. This perspective summarises the recent trends of developing lubricants and greases for electric vehicles.