bluuebunny/crossref_metadata_2025 huggingface dataset:
A physiological signal derived from sun-induced chlorophyll fluorescence quantifies crop physiological response to environmental stresses in the U.S. Corn Belt
Authors: Kimm Hyungsuk , Guan Kaiyu , Jiang Chongya , Miao Guofang , Wu Genghong , Suyker Andrew E , Ainsworth Elizabeth A , Bernacchi Carl J , Montes Christopher M , Berry Joseph A , Yang Xi , Frankenberg Christian , Chen Min , Köhler Philipp
Published: November 2021

Sun-induced chlorophyll fluorescence (SIF) measurements have shown unique potential for quantifying plant physiological stress. However, recent investigations found canopy structure and radiation largely control SIF, and physiological relevance of SIF remains yet to be fully understood. This study aims to evaluate whether the SIF-derived physiological signal improves quantification of crop responses to environmental stresses, by analyzing data at three different spatial scales within the U.S. Corn Belt, i.e. experiment plot, field, and regional scales, where ground-based portable, stationary and space-borne hyperspectral sensing systems are used, respectively. We found that, when controlling for variations in incoming radiation and canopy structure, crop SIF signals can be decomposed into non-physiological (i.e. canopy structure and radiation, 60% ∼ 82%) and physiological information (i.e. physiological SIF yield, ΦF, 17% ∼ 31%), which confirms the contribution of physiological variation to SIF. We further evaluated whether ΦF indicated plant responses under high-temperature and high vapor pressure deficit (VPD) stresses. The plot-scale data showed that ΦF responded to the proxy for physiological stress (partial correlation coefficient, r
p= 0.40, p< 0.001) while non-physiological signals of SIF did not respond (p> 0.1). The field-scale ΦF data showed water deficit stress from the comparison between irrigated and rainfed fields, and ΦF was positively correlated with canopy-scale stomatal conductance, a reliable indicator of plant physiological condition (correlation coefficient r= 0.60 and 0.56 for an irrigated and rainfed sites, respectively). The regional-scale data showed ΦF was more strongly correlated spatially with air temperature and VPD (r= 0.23 and 0.39) than SIF (r= 0.11 and 0.34) for the U.S. Corn Belt. The lines of evidence suggested that ΦF reflects crop physiological responses to environmental stresses with greater sensitivity to stress factors than SIF, and the stress quantification capability of ΦF is spatially scalable. Utilizing ΦF for physiological investigations will contribute to improve our understanding of vegetation responses to high-temperature and high-VPD stresses.
Observation of aerosol induced ‘lower tropospheric cooling’ over Indian core monsoon region
Authors: Jangid Manish , Mishra Amit Kumar , Koren Ilan , Sarangi Chandan , Kumar Krishan , Singh Sachchidanand , Tripathi Sachchidanand
Published: November 2021

Aerosols play a significant role in regional scale pollution that alters the cloud formation process, radiation budget, and climate. Here, using long-term (2003–2019) observations from multi-satellite and ground-based remote sensors, we show robust aerosol-induced instantaneous daytime lower tropospheric cooling during the pre-monsoon season over the Indian core monsoon region (ICMR). Quantitatively, an average cooling of −0.82 °C ± 0.11 °C to −1.84 °C ± 0.25 °C is observed in the lower troposphere. The observed cooling is associated with both aerosol-radiation and aerosol-cloud-radiation interaction processes. The elevated dust and polluted-dust layers cause extinction of the incoming solar radiation, thereby decreasing the lower tropospheric temperature. The aerosol-cloud interactions also contribute to enhancement of cloud fraction which further contributes to the lower tropospheric cooling. The observed cooling results in a stable lower tropospheric structure during polluted conditions, which can also feedback to cloud systems. Our findings suggest that aerosol induced lower tropospheric cooling can strongly affect the cloud distribution and circulation dynamics over the ICMR, a region of immense hydroclimatic importance.
Lattice star and acyclic branched polymer vertex exponents in 3d
Authors: Campbell S , Janse van Rensburg EJ
Published: November 2021

Numerical values of lattice star entropic exponents γ

f
, and star vertex exponents σ

f
, are estimated using parallel implementations of the PERM and Wang–Landau algorithms. Our results show that the numerical estimates of the vertex exponents deviate from predictions of the ϵ-expansion and confirms and improves on estimates in the literature. We also estimate the entropic exponents

γ

G

of a few acyclic branched lattice networks with comb and brush connectivities. In particular, we confirm within numerical accuracy the Duplantier scaling relation

γ

G

−
1
=

∑

f
⩾
1

m

f

σ

f

for a comb and two brushes (where m

f
is the number of nodes of degree f in the network) using our independent estimates of σ

f
.
Interfacial structure and mechanical properties of the Ta/Re layered composites prepared by chemical vapor deposition
Authors: Yuan Zhentao , Chen Jingchang , Wei Yan , Hu Changyi , Luo Yuan , Chen Li , Cai Hongzhong , Wang Xiao
Published: November 2021

A novel Ta/Re layered composites with high temperature resistance, low cost, light weight, and excellent mechanical properties has been prepared by chemical vapor deposition, for improving the comprehensive service performance of the aerospace engine nozzle materials. The interface structure, element distribution, and mechanical properties of the Ta/Re layered composites have been studied with scanning electron microscopy, energy dispersive spectroscopy, x-ray diffraction, and tensile testing machine. The results show that the structure of the Ta/Re layered composites is flat and smooth, uniform, and dense. Further, the interface joint is a serrated meshing structure, which tremendously improves the interface bonding properties. The high temperature (1600 °C) tensile strength of the heat-treated Ta/Vol. 30% Re layered composites is 125 MPa, which is 2.8 times and 56.3% higher than the commonly used nozzle materials C103 and Nb521, respectively, whereas the raw material cost is only about 46% of that of pure rhenium. The heat treatment process enhances the mutual diffusion behavior of the atoms in the interface diffusion layer, and increases the thickness of the diffusion layer, besides changing the mechanical properties of the material. When the heat treatment process is at 1800 °C × 1 h, the highest tensile strength at room temperature is 739.61 MPa, which is 42.76% higher than that in a deposited state. This work can provide a reference for the further research of the Ta/Re layered composites.
Detection of transcription factors binding to methylated DNA by deep recurrent neural network
Authors: Li Hongfei , Gong Yue , Liu Yifeng , Lin Hao , Wang Guohua
Published: November 2021

Transcription factors (TFs) are proteins specifically involved in gene expression regulation. It is generally accepted in epigenetics that methylated nucleotides could prevent the TFs from binding to DNA fragments. However, recent studies have confirmed that some TFs have capability to interact with methylated DNA fragments to further regulate gene expression. Although biochemical experiments could recognize TFs binding to methylated DNA sequences, these wet experimental methods are time-consuming and expensive. Machine learning methods provide a good choice for quickly identifying these TFs without experimental materials. Thus, this study aims to design a robust predictor to detect methylated DNA-bound TFs. We firstly proposed using tripeptide word vector feature to formulate protein samples. Subsequently, based on recurrent neural network with long short-term memory, a two-step computational model was designed. The first step predictor was utilized to discriminate transcription factors from non-transcription factors. Once proteins were predicted as TFs, the second step predictor was employed to judge whether the TFs can bind to methylated DNA. Through the independent dataset test, the accuracies of the first step and the second step are 86.63% and 73.59%, respectively. In addition, the statistical analysis of the distribution of tripeptides in training samples showed that the position and number of some tripeptides in the sequence could affect the binding of TFs to methylated DNA. Finally, on the basis of our model, a free web server was established based on the proposed model, which can be available at https://bioinfor.nefu.edu.cn/TFPM/.
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies
Authors: de Zwart Auke , Riezebos-Brilman Annelies , Lunter Gerton , Vonk Judith , Glanville Allan R , Gottlieb Jens , Permpalung Nitipong , Kerstjens Huib , Alffenaar Jan-Willem , Verschuuren Erik
Published: November 2021

Background

Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.

Methods

Relevant databases were queried and study outcomes extracted using a standardized method and summarized.

Results

Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0–3%), but CLAD progression 180–360 days postinfection was substantial (pooled incidences 19–24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27–1.18]), although results were highly variable between studies.

Conclusions

RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
An inverse DEA model for intermediate and output target setting in serially linked general two-stage processes
Authors: Kazemi Ahmad , Galagedera Don U A
Published: November 2021

In this paper, we formulate an inverse data envelopment analysis (DEA) model for a serially linked two-stage production process operating under constant returns to scale technology. The inverse DEA model determines a set of intermediate and output targets for an input augmented decision-making unit (DMU) to maintain its relative efficiency at a pre-specified level. We solve the inverse DEA model using the constraint method used in multi-objective optimization. The input augmented DMU with intermediate and output targets obtained in the inverse DEA model is a hypothetical DMU. Under our modelling framework, when such a hypothetical DMU established on an inefficient DMU is included in the observed DMU set, the frontier established with observed DMU set remains intact. This is important in practice as the intermediate and output targets of the hypothetical DMU would be feasible. When overall efficiency of the hypothetical DMU is decomposed, individual stages have the same efficiency level as that of the hypothetical DMU. This is important to DMU managers as sub-processes also maintain the desired overall efficiency level. We apply our inverse DEA model to a sample of Australian superannuation funds. We demonstrate that each unique Pareto optimal solution of the inverse DEA model obtained through the constraint method provides a specific set of intermediate and output targets and they may offer trade-off between intermediates and outputs. When fund managers anticipate expansion or growth in their funds, choice of targets allows comparison of different trade-off scenarios and makes informed decisions.
Performance of Japanese patients in registrational studies
Authors: Goto Yasushi , Arakawa Sayaka , Shirasawa Masayuki , Higashiyama Ryoko , Baba Keisuke , Masuda Ken , Shinno Yuki , Matsumoto Yuji , Okuma Yusuke , Yoshida Tatsuya , Horinouchi Hidehito , Yamamoto Noboru , Ohe Yuichiro
Published: November 2021

Introduction

The accelerated development of lung cancer treatments has resulted in a single global study that is sufficient for a new agent and indication to be approved. Not all new treatments predominate globally, and differences in standards of care may influence the efficacy of treatments in the real world.

Methods

The results from Japanese domestic trials and global trials that included a subset population of Japanese patients were evaluated for 18 genomic targeted agents and immune therapies approved after 2000. The results were collected from drug applications that were reviewed for treatment approval in Japan.

Results

Japan is one of the first countries to approve and fully reimburse new agents around the world. Alectinib and nivolumab, which were first developed by Japanese pharmaceutical companies, were evaluated in an independent domestic trial, which resulted in their early approval. For most other indications, 1.1–15.8% of the patients who participated in pivotal registration studies were Japanese, and their treatment results were comparable to those of the overall population. Overall survival was less likely to be improved by four agents for which the post-protocol therapy might have been different in Japan than in other countries.

Conclusions

Overall, a positive result in a global trial was emulated in Japanese patients and led to the approval of a new standard treatment in Japan. Early approvals were attained by either participating in the global registrational study or conducting a domestic phase II study. The higher efficacy of new agents may be an issue in the future, as Japanese patients had early access to the new agent and may receive better treatment after the trial.
Clinical relevance of addition of conventional treatment to concurrent chemoradiotherapy in patients with FIGO stage III–IV cervical cancer: a retrospective analysis of a Japanese cohort
Authors: Kurosu Hiroyuki , Todo Yukiharu , Yamada Ryutaro , Minowa Kaoru , Tsuruta Tomohiko , Minobe Shinichiro , Nishiyama Noriaki , Kato Hidenori
Published: November 2021

Background

Concurrent chemoradiotherapy has limited therapeutic efficacy for stage III–IV cervical cancer. We aimed to identify a subgroup of patients with stage III–IV cervical cancer who benefit from concurrent chemoradiotherapy with additional treatment.

Methods

We retrospectively reviewed 120 patients with stage III–IV cervical cancer who were treated with concurrent chemoradiotherapy from 2002 to 2018. We compared overall survival between patients treated with concurrent chemoradiotherapy alone and those who received concurrent chemoradiotherapy with additional conventional treatments (systemic chemotherapy before and/or after concurrent chemoradiotherapy and/or extended-field radiation). Prognostic factors were statistically analysed.

Results

Overall, 44 (36.7%) and 21 (17.5%) patients were radiologically diagnosed with pelvic and para-aortic lymph node enlargement, respectively. The median tumour diameter was 5.7 cm. A total of 69 (57.5%) patients received no additional treatment, and 51 (42.5%) received additional treatment. Cox regression analysis identified the following prognostic factors: histological non-squamous cell carcinoma (hazard ratio, 3.9; 95% confidence interval, 1.8–8.2), tumour diameter of ≥6 cm (hazard ratio, 2.1; 95% confidence interval, 1.2–3.7), radiological pelvic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1–4.0) and radiological para-aortic lymph node enlargement (hazard ratio, 2.1; 95% confidence interval, 1.1–4.1). Even in the lowest risk group (no risk factors), the 5-year overall survival rate was lower in the additional treatment group than in the concurrent chemoradiotherapy alone group (78.7% vs. 80.9%, respectively; log-rank test, P = 0.79).

Conclusions

Addition of conventional treatments to concurrent chemoradiotherapy might not improve survival in patients with advanced cervical cancer. Novel treatment strategies including immune checkpoint inhibitors should be considered for such patients.
Pif1 Helicases and the Evidence for a Prokaryotic Origin of Helitrons
Authors: Heringer Pedro , Kuhn Gustavo C S
Published: November 2021

Helitrons are the only group of rolling-circle transposons that encode a transposase with a helicase domain (Hel), which belongs to the Pif1 family. Because Pif1 helicases are important components of eukaryotic genomes, it has been suggested that Hel domains probably originated after a host eukaryotic Pif1 gene was captured by a Helitron ancestor. However, the few analyses exploring the evolution of Helitron transposases (RepHel) have focused on its Rep domain, which is also present in other mobile genetic elements. Here, we used phylogenetic and nonmetric multidimensional scaling analyses to investigate the relationship between Hel domains and Pif1-like helicases from a variety of organisms. Our results reveal that Hel domains are only distantly related to genomic helicases from eukaryotes and prokaryotes, and thus are unlikely to have originated from a captured Pif1 gene. Based on this evidence, and on recent studies indicating that Rep domains are more closely related to rolling-circle plasmids and phages, we suggest that Helitrons are descendants of a RepHel-encoding prokaryotic plasmid element that invaded eukaryotic genomes before the radiation of its major groups. We discuss how a Pif1-like helicase domain might have favored the transposition of Helitrons in eukaryotes beyond simply unwinding DNA intermediates. Finally, we demonstrate that some examples in the literature describing genomic helicases from eukaryotes actually consist of Hel domains from Helitrons, a finding that underscores how transposons can hamper the analysis of eukaryotic genes. This investigation also revealed that two groups of land plants appear to have lost genomic Pif1 helicases independently.
Population Histories and Genomic Diversity of South American Natives
Authors: Castro e Silva Marcos Araújo , Ferraz Tiago , Couto-Silva Cainã M , Lemes Renan B , Nunes Kelly , Comas David , Hünemeier Tábita
Published: November 2021

South America is home to one of the most culturally diverse present-day native populations. However, the dispersion pattern, genetic substructure, and demographic complexity within South America are still poorly understood. Based on genome-wide data of 58 native populations, we provide a comprehensive scenario of South American indigenous groups considering the genomic, environmental, and linguistic data. Clear patterns of genetic structure were inferred among the South American natives, presenting at least four primary genetic clusters in the Amazonian and savanna regions and three clusters in the Andes and Pacific coast. We detected a cline of genetic variation along a west-east axis, contradicting a hard Andes-Amazon divide. This longitudinal genetic variation seemed to have been shaped by both serial population bottlenecks and isolation by distance. Results indicated that present-day South American substructures recapitulate ancient macroregional ancestries and western Amazonia groups show genetic evidence of cultural exchanges that led to language replacement in precontact times. Finally, demographic inferences pointed to a higher resilience of the western South American groups regarding population collapses caused by the European invasion and indicated precontact population reductions and demic expansions in South America.
Rice as a vehicle for micronutrient fortification: a systematic review of micronutrient retention, organoleptic properties, and consumer acceptability
Authors: Pyo Euisun , Tsang Becky L , Parker Megan E
Published: November 2021

Context

Previous reviews have focused on evaluating the efficacy and effectiveness of rice fortification, despite the need to also understand the outcomes of micronutrient retention, organoleptic properties, and acceptability to inform nutrition programs.

Objective

This systematic review aims to consolidate existing evidence on micronutrient retention, organoleptic properties, and acceptability of fortified rice.

Data Sources

Eligible articles were identified from 22 electronic databases and personal referrals and reviews.

Study Selection

Studies on rice fortified via extrusion or coating technologies were included in the review if they reported outcomes in at least 1 of 3 domains: micronutrient retention, organoleptic or physicochemical properties, and acceptability (evaluated by sensory tests and consumer surveys). Any years of publication and study populations were considered for inclusion. A total of 15 391 articles were screened, yielding 49 for inclusion.

Data Extraction

Study results were summarized descriptively through discussions by intervention conditions, study population, measurement methods, and key findings. The included studies were independently reviewed by 2 of the 3 authors, and all 3 authors reached consensus on the quality and major findings from the included articles.

Results

Extrusion and coating fortification technologies were found to be comparable across studies that assessed retention, organoleptic properties, and acceptability. Cooking fortified rice in excess water increased micronutrient loss for both technologies. Fortified kernels containing ferric pyrophosphate, zinc oxide, or zinc sulfate showed the most positive results for all outcomes reviewed, while retention rates of vitamin A in multiple-micronutrient-fortified rice were variable.

Conclusions

The current practice of fortifying rice with ferric pyrophosphate provides high micronutrient stability and results in rice with organoleptic properties and consumer acceptance levels comparable to those of unfortified milled rice, although it presents challenges regarding the effect of vitamin A–fortified rice on vitamin A status.
The Incidence of Iliac Screw-Related Complications After Long Fusion Surgery in Patients with Adult Spinal Deformity
Authors: Banno Tomohiro , Hasegawa Tomohiko , Yamato Yu , Yoshida Go , Arima Hideyuki , Oe Shin , Mihara Yuki , Ide Koichiro , Watanabe Yuh , Kurosu Kenta , Nakai Keiichi , Matsuyama Yukihiro
Published: November 2021

Study Design.

Retrospective study.

Objective.

To investigate the long-term clinical outcome and incidence of iliac screw-related complications in patients with adult spinal deformity (ASD).

Summary of Background Data.

Rigid lumbosacral fixation is crucial to achieve optimal global alignment and successful long-term clinical outcomes.

Methods.

The data of eligible patients with ASD who underwent spinopelvic fixation using bilateral iliac screws with at least 5-year follow-up periods were retrospectively analyzed. Iliac screw loosening and rod breakage between the S1 and iliac (S1/IL) screws were defined as distal instability (DI). Demographic data, health-related quality of life scores, and spinopelvic parameters in the DI group were compared with those in the non-DI group. Sub-group analyses were performed between the cases with and without alignment change after rod fracture at S1/IL.

Results.

Of the 159 patients, the data of 110 patients (15 men, 95 women; mean age, 67.8 yr) were analyzed. The follow-up rate was 69%. Forty-five (41%) patients showed DI (29 cases [26%] in screw loosening, 16 cases [15%] in rod breakage). Eight patients (7.3%) required revision surgery because of iliac screw-related complications. No significant differences were observed in the Oswestry Disability Index and Scoliosis Research Society questionnaire (revised) scores between the DI and non-DI groups. The patients with iliac screw loosening showed significantly greater values of preoperative pelvic incidence, pelvic tilt (PT), and postoperative PT, and T1-pelvic angle. In patients with rod breakage at S1/IL, five patients (31%) who had associated mechanical complications showed an alignment change between pre and post rod breakage. They showed significantly higher and lower rates of high-grade osteotomies and L5/S interbody fusion, respectively.

Conclusion.

The incidence rate of iliac screw-related complications was relatively high. However, they had a little effect on sagittal alignment deterioration and there were few cases that required revision surgery.

Level of Evidence: 4
Mismatch Between Pelvic Incidence and Lumbar Lordosis is the Key Sagittal Plane Determinant of Patient Outcome at Minimum 40 Years After Instrumented Fusion for Adolescent Idiopathic Scoliosis
Authors: Rubery Paul T. , Lander Sarah T. , Mesfin Addisu , Sanders James O. , Thirukumaran Caroline P.
Published: November 2021

Study Design.

Retrospective review

Objective.

Assess measures of spinal-pelvic balance in predicting functional outcome in patients who underwent posterior spinal fusion for adolescent idiopathic scoliosis (AIS) at minimum 40-year follow-up.

Summary of Background Data.

Back pain and long-term function are considered when choosing levels for surgery in AIS patients. Three hundred and fourteen patients underwent fusion for AIS between 1961 and 1977. One hundred and thirty-four patients were located for potential long-term follow-up.

Methods.

With Institutional Review Board approval, medical records and public resources were used to locate patients. Patients completed health-related quality of life (HRQoL) instruments, and returned for assessment including full radiographs. Radiographs were analyzed for scoliosis measures, and recognized spinal-pelvic measures including the lumbar lordosis, sagittal vertical axis (SVA), pelvic incidence, and pelvic tilt (PT). Bivariate and multivariable analyses were performed to assess the association between spinal-pelvic measures and patient-reported outcomes.

Results.

Thirty-five of 134 patients agreed to return for complete HRQoL and radiographic follow-up. There were no differences at baseline between those agreeing and declining participation. The cohort was 94% female, had an average age of 60.5 years, and average follow-up of 46 years. In bivariate analysis, pelvic incidence and lumbar lordosis difference (PI-LL) was the only spinal-pelvic parameter which statistically discriminated between patients doing well and not, as assessed by the Oswestry Disability Index and the Patient-reported Outcomes Measurement Information System (PROMIS) Pain Interference and Fatigue instruments. In multivariable analysis, (PI-LL > 9°) was associated with worse scores in PROMIS-Pain Interference, Physical Function, Depression, Fatigue, Social Function and the total Oswestry score. An SVA > 50 mm was associated with worse scores in the Scoliosis Research Society-7.

Conclusion.

In a cohort of 35 patients with average follow-up of 46 years after posterior spinal instrumentation with Harrington rods (PSIF) for AIS, spinal-pelvic mismatch as identified by (PI-LL > 9°) was associated with inferior HRQoL outcomes. Other spinal-pelvic measures (SVA and PT) were not reliably associated with inferior HRQoL.

Level of Evidence: 4
The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Authors: Delgado Julio , Papadouli Irene , Sarac Sinan B. , Moreau Alexandre , Hovgaard Doris , Gisselbrecht Christian , Enzmann Harald , Pignatti Francesco
Published: November 2021

Tafasitamab is a humanized monoclonal antibody that binds to the CD19 antigen, which is expressed in tumor cells from patients with diffuse large B-cell lymphoma (DLBCL). On June 24, 2021, a positive opinion for a conditional marketing authorization was issued by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) for tafasitamab, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory DLBCL who are ineligible for autologous stem cell transplantation. Tafasitamab was evaluated in the phase 2 single-arm, multicenter, open-label L-MIND clinical trial. The primary endpoint of this trial was objective response rate (ORR). The best ORR, achieved at any time during the study, was 56.8% (95% confidence interval: 45.3%–67.8%), and the median duration of response was 34.6 months (95% confidence interval: 26.1–not reached). The most frequently reported adverse events by system organ class were infections and infestations (72.8%; grade ≥3: 29.6%), blood and lymphatic system disorders (65.4%; grade ≥3: 56.8%), gastrointestinal disorders (64.2%; grade ≥3: 2.5%), and general disorders and administration site conditions (58.0%; grade ≥3: 8.6%). The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the CHMP.
Managing job stress among teachers of children with autism spectrum disorders
Authors: Akanaeme Immaculata N. , Ekwealor Felicia Ngozi , Ifeluni Clara N. , Onyishi Charity N. , Obikwelu Chizoba L. , Ohia Nkiru Christiana , Obayi Loveline N. , Nwaoga Chinyere Theresa , Okafor Agnes E. , Victor-Aigbodion Vera , Ejiofor Toochukwu E. , Afiaenyi Ifeoma C. , Ekomaru Chinyere I. , Dike Ibiwari Caroline
Published: November 2021

Background:

Job-related stress undermines occupational, personal, and organizational outcomes. Stress symptoms are common among teachers of children with autism spectrum disorders and affect the academic progress of the children. This study investigated the effectiveness of yoga-based cognitive behavioral therapy in reducing occupational stress among teachers of children with autism in Lagos states, Nigeria.

Methods:

The current study adopted a group-randomized waitlist control (WLC) trial design with pre-test, posttest, and follow-up assessments. Participants included 58 teachers of children with autism in public and private special schools in Lagos state. Participants were randomly assigned to combined cognitive behavioral therapy and yoga (Y-CBT) (N = 29) and WLC (N = 29) groups. The Y-CBT group participated in a 2 hours Y-CBT program weekly for 12 weeks. Three instruments – Demographic Questionnaire, Single-Item Stress Questionnaire, and Teachers’ Stress Inventory (TSI) were used to collect data. Data were collected at baseline; posttest and follow-up evaluations. Data were analyzed using means, standard deviations, t test statistics, repeated measures analysis of variance, and bar charts.

Results:

Results revealed that all dimensions of job stress (perception of stress sources, stress manifestation, and total TSI scores) reduced significantly at posttest and follow up assessments among the Y-CBT group, compared to the WLC.

Conclusion:

It was concluded that Y-CBT modalities could help to minimize the perception of stress sources and stress manifestation as well as total TSI scores among teachers of children with autism spectrum disorders.
Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma
Authors: Qu Meng-Meng , Zhu Yuan-Hui , Li Yi-Xiang , Li Zhi-Fan , Li Jin-Kui , Xu Yong-Sheng , Shrestha Manishkumar , Lei Jun-Qiang
Published: November 2021

Rationale:

Presence of synchronous double hepatocelluar carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (sdpHCC-ICC) located separately within a single liver is extremely rare. The purpose of this study is to investigate the clinical, imaging, pathological characteristics, and prognosis of patients with sdpHCC-ICC, in order to enhance our understanding of the disease and improve diagnostic and therapeutic effect.

Patient concerns:

A 49-year-old, female with the diagnosis of hepatitis B virus with obvious liver cirrhosis, was admitted to our hospital. On admission, the levels of α-fetoprotein and carbohydrate antigen 19-9 were found to be elevated. Abdominal ultrasonography and enhanced computed tomography revealed 2 solid masses located in segments (S) 4 and 6 of the liver, with malignant behaviors.

Diagnoses:

In the light of above investigations, preoperative diagnosis of multiple primary hepatocellular carcinomas was made.

Intervention:

Hepatic resection of both segments was done. The resected specimens revealed the presence of well-defined tumors in segments 4 and 6 measuring 5.0 cm and 2.5 cm respectively.

Outcomes:

Histopathological examination confirmed the tumor of the 4th segment to be moderately and poorly differentiated ICC, and the tumor of the 6th segment to be poorly differentiated HCC. Immunohistochemically, the ICC in S4 was positive for CK19 and negative for Heppar-1, whereas the HCC in S6 was positive for Heppar-1 and negative for CK19. Unfortunately, metastasis to multiple organs and lymph nodes were observed 3 months later. The patient died of liver failure 16 months after surgery.

Lessons:

The clinical characteristics of sdpHCC-ICC are usually atypical and nonspecific making its preoperative diagnosis quite difficult. Hepatitis B virus and hepatitis C virus infection were both the independent risk factor for the development of sdpHCC-ICC. In patients with chronic liver disease, careful observation with imaging is of utmost necessity. Tumor markers may also play a valuable role in the diagnosis. The definite diagnosis depends on pathological examination. Hepatic resection is considered the most effective mode of treatment. The prognosis of synchronous occurrence of double hepatic cancers is worse than either HCC or ICC, and the origin of the disease needs further study.
Nomogram to predict contralateral breast cancer risk in breast cancer survivors
Authors: Tong Jiaci , Tan Dewei , Ma Jing , Hu Ye , Li Man
Published: November 2021

The main purpose of this study was to build a prediction model for patients with contralateral breast cancer (CBC) using competing risks methodology. The aim is to help clinicians predict the probability of CBC in breast cancer (BC) survivors.

We reviewed data from the Surveillance, Epidemiology, and End Results database of 434,065 patients with BC. Eligible patients were used to quantify the association between the development of CBC and multiple characteristics of BC patients using competing risk models. A nomogram was also created to facilitate clinical visualization and analysis. Finally, the stability of the model was verified using concordance index and calibration plots, and decision curve analysis was used to evaluate the clinical utility of the model by calculating the net benefit.

Four hundred thirty-four thousand sixty-five patients were identified, of whom 6944 (1.6%) developed CBC in the 10 years follow-up. The 10-year cumulative risk of developing CBC was 2.69%. According to a multivariate competing risk model, older patients with invasive lobular carcinoma who had undergone unilateral BC surgery, and whose tumor was better differentiated, of smaller size and ER-negative/PR-positive, had a higher risk of CBC. The calibration plots illustrated an acceptable correlation between the prediction by nomogram and actual observation, as the calibration curve was closed to the 45° diagonal line. The concordance index for the nomogram was 0.65, which indicated it was well calibrated for individual risk of CBC. Decision curve analysis produced a wide range of risk thresholds under which the model we built would yield a net benefit.

BC survivors remain at high risk of developing CBC. Patients with CBC have a worse clinical prognosis compared to those with unilateral BC. We built a predictive model for the risk of developing CBC based on a large data cohort to help clinicians identify patients at high risk, which can then help them plan individualized surveillance and treatment.
HIST3H2A is a potential biomarker for pancreatic cancer
Authors: Zhao Mengyu , Dai Rongyang
Published: November 2021

The family of histone H2A proved that there are a lot of variants associated with cancer development. The link between HIST3H2A and pancreatic cancer has never been noted before. Our research suggests that HIST3H2A affects pancreatic tumor immune process and prognosis of patients, through the JAK STAT pathway, so it is expected to become the biomarker of pancreatic cancer.

Gene expression profiles and clinical data of pancreatic cancer patients were downloaded from The Cancer Genome Atlas database (TCGA) and The Genotype Tissue Expression (GETx) project. R software (Rx64 3.6.0) was utilized to analyze. Gene set enrichment analysis (GSEA) was used to analyze HIST3H2A related signaling pathways in pancreatic cancer. CIBERSORT is applied to estimate the compositional patterns of the 22 types of immune cell fraction based on bulk expression data.

HIST3H2A was expressed at higher in pancreatic cancer tissues than normal pancreatic tissues. Kaplan–Meier survival analysis suggested that the level of HIST3H2A expression affect prognosis of pancreatic cancer patients. Univariate Cox analysis and Multivariate Cox analysis suggested that HIST3H2A expression is a prognostic factor of pancreatic cancer. Cor expression analysis indicated that the genes positively correlated with HIST3H2A expression trend were DCST1-AS1, HIST1H2BD, SLC12A9-AS1. GSEA showed that the JAK-STAT signaling pathway was enriched in the HIST3H2A high expression phenotype, whereas intestinal network for IgA production, Asthma and Chemokine signaling pathway were enriched in the HIST3H2A low expression phenotype. In additional, results showed that CD8 T cells (P = .007), activated CD4 memory T cells (P = .001), and monocytes (P = .002) were more abundant in lower HIST3H2A expression groups.

HIST3H2A is a promising biomarker for predicting prognosis of pancreatic cancer, and it could be a potential therapeutic target. HIST3H2A might regulate the progression of tumor immune in pancreatic cancer through modulating the JAK-STAT pathway. In addition, the role HIST3H2A in pancreatic cancer may be related to DCST1-AS1, HIST1H2B, SLC12A9-AS1. However, more research is necessary to validate findings.
Endoscopic removal of accidental aspirated and ingested dental foreign bodies
Authors: Hayashi Hiroki , Abe Atsushi , Ota Mitsuhiko , Momokita Moeko , Ishihama Takanori , Furuta Hiroshi , Taniguchi Toru , Takeuchi Kazuo
Published: November 2021

The incidence of accidental ingestion and aspiration of foreign body (FB) is likely to occur. Many FBs are discharged spontaneously, but many dental FBs are often sharp and may remain in the pharynx, esophagus, and stomach, causing serious complications such as hemorrhage, asphyxia, perforation of the digestive tract, mediastinal emphysema, peritonitis, and ileus. We aimed to examine which type of dental foreign bodies can be removed by endoscope.

In this study, we enrolled 32 patients who were evaluated at the Emergency and Critical Center between January 2014 and December 2019 and who accidentally ingested or aspirated dental FBs. Medical records were reviewed to determine the patients’ sex, age, medical history, time from accidental ingestion of a FB to consultation, cause, location, occurrence status, nature of the FB, location of retained FB, treatment, complications, and outcome.

We enrolled 32 patients (14 men, 18 women), with a mean age of 74.5 ± 12.8 years. Accidental ingestion at treatment was common. The most frequent site where the FB was retained was upper gastrointestinal tract (26 cases, 81.3%). In this study, endoscopic removal was indicated for dentures under the size of 43.3 mm, for dental FB (except dentures) more than 13.6 mm. In dentures, between the number of missing teeth, clasp, type, and endoscopic removal was not statistically significant.

Dentures under the size of 43.3 mm was likely to be removed by endoscope. Dental FB (except dentures) more than the size of 13.6 mm was likely to be removed by endoscope. There were no indications for endoscopic removal except for size.
Evaluation of the cross-sectional area of small pulmonary vessels in the diagnosis of chronic obstructive pulmonary disease by quantitative computed tomography
Authors: Wang Yifan , Su Tong , Feng Shaotong , Chen Juan , Tian Xingcang , Zhu Li
Published: November 2021

Patients with chronic obstructive pulmonary disease (COPD) have a reduced cross-sectional area (CSA) of small pulmonary vessels and decreased pulmonary function test (PFT) indexes. This study investigated the value of small pulmonary vessel CSA in diagnosing and evaluating the severity of COPD and its correlation with PFT.

This retrospective case-control study included patients with COPD who underwent multi-slice spiral computed tomography (CT) between March 2015 and December 2018. COPD severity was graded. Patients with normal CT results were included as controls. The CSA of small pulmonary vessels at the sub-segmental (5–10 mm2) and sub-sub-segmental (<5 mm2) levels was measured. Receiver operating characteristic (ROC) curves were used to evaluate the effect of CSA for COPD risk prediction. The correlation between CSA% and PFT indexes was evaluated.

There were 124 and 106 patients in the COPD and control groups, respectively. The %CSA <5 and %CSA5–10 were smaller in the COPD group than in controls (P 
< .05). The %CSA <5 in each subgroup stratified by COPD severity was smaller than in controls (P 
< .05). The % CSA5–10 was significantly smaller in the moderate and severe groups than in controls (P 
< .05). At 0.655%CSA <5 cut-off, the ROC area under the curve (AUC) was 0.765. For %CSA5–10, a 0.565 cut-off led to an AUC of 0.752. Both %CSA <5 and %CSA5–10 were positively correlated with all PFT indexes (r = 0.180–0.462, all P 
< .05).

CSA was positively correlated with PFT. Analysis of small pulmonary vessel CSA based on CT images contributes to diagnosing and assessing the severity of COPD.
Association between APE1 rs1760944 and rs1130409 polymorphism with prostate cancer risk
Authors: Liu Jinnian , Zheng Jian , Guo Yu , Sheng Xia , Yin Yongjian , Qian Shengqiang , Xu Bin , Xiong Wei , Yin Xiangrui
Published: November 2021

Background:

Recently, some studies have suggested that the association of apurinic/apyrimidinic endonuclease 1 (APE1) gene polymorphism with prostate cancer (PCa) risk, but there are still some controversies. Hence, we elaborated the relationship between APE1 rs1760944 and rs1130409 gene and PCa risk through systematic literature review and meta-analysis.

Methods:

As of March 2020, EMBASE, PubMed, the Cochrane Library, Science Direct/Elsevier, MEDLINE and CNKI were used for systematic literature retrieval to investigate the correlation between APE1 rs1760944 and rs1130409 gene polymorphism with PCa risk. Meta-analysis was performed using Review Manager and Stata software.

Results:

Seven studies were distinguished, consists of 1769 cases of PCa patients and 2237 normal controls. Our results illustrated that there are significant correlation between the APE1 rs1760944 gene polymorphism and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 0.62, 95%, CI [0.39, 0.97]); Codominant model (ORs 0.74, 95% CI [0.58, 0.95]); Dominant model (ORs 0.75, 95%, CI [0.59, 0.95]); Recessive model (ORs 0.63, 95% CI [0.41, 0.96]); Allele model (ORs 0.78, 95% CI [0.65, 0.94]). There also have significant associations between APE1 rs1130409 polymorphisms and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 1.37, 95%, CI [1.01, 1.85]); Codominant model (ORs 1.21, 95% CI [1.01, 1.44]); Dominant model (ORs 1.33, 95%, CI [1.02, 1.73]); Recessive model (ORs 1.74, 95% CI [1.06, 2.85]); Allele model (ORs 1.14, 95% CI [1.00, 1.29]).

Conclusion:

This study suggests that APE1 rs1760944 polymorphisms might be a protective factor of PCa, and APE1 rs1130409 is suggested to be a risk factor of PCa. APE1 rs1760944 and rs1130409 polymorphisms may be used in the risk assessment of PCa.
DDX10 and BYSL as the potential targets of chondrosarcoma and glioma
Authors: Quan Xuemin , Zhao Changsong , Gao Zhengrong , Zhang Yao , Zhao Rugang , Wang Jingjing , Zhang Qiang
Published: November 2021

To provide reliable molecular markers and effective therapeutic targets for chondrosarcoma and glioma.

Gene Set Enrichment (GSE) 29745 and GSE48420 were downloaded from the Gene Expression Omnibus (GEO) database. Differently expressed genes (DEGs) were identified by the GEO2R. We annotated the function of common DEGs through Digital Audio/Video Interactive Decoder (DAVID) and Metascape. Protein–protein interaction network construction was performed through STRING. Hub genes were identified by the two different algorithms (MCC, EPC). DDX10 and BYSL were key factors in embryo implantation and development, and plays a role in a variety of cancers. The role of the DDX10 and BYSL on the glioma derived from the chondrosarcoma would be explored by the clinical samples.

A total of 1442 DEGs were identified. The variations in DEGs were mainly enriched in vasculature development, cell motion, blood vessel development, cell migration, regulation of cell proliferation, regulation of cell proliferation, wound healing, biological adhesion, growth factor binding, identical pathways in cancer, and p53 signaling pathway. Dead-box helicase 10 (DDX10), Bystin-like (BYSL), and WD repeat domain 12 (WDR12) were identified as the hub genes, and the three hub genes were up-regulated in the chondrosarcoma. Chondrosarcoma patients with high expression levels of DDX10 (Logrank P = .0052; HR (high) = 1.8; n (high) = 131, 50%), and BYSL (P = 6.5e-05; HR (high) = 2.3; n (high) = 131, 50%) had poorer overall survival times than those with low expression levels.

DDX10 and BYSL genes may provide reliable molecular markers and effective therapeutic targets for chondrosarcoma and glioma.
Prediction of liver stiffness by serum indexes in HCV-infected patients with or without HIV coinfection
Authors: Merchante Nicolás , Mena Álvaro , Pascasio Juan-Manuel , Marco Andrés , Rodriguez Manuel , Hernandez-Guerra Manuel , Simón Miguel-Angel
Published: November 2021

Identification of advanced fibrosis/cirrhosis in hepatitis C virus (HCV)-infected patients should be a mainstay before starting treatment; however, the limited access of many centres to transient elastography (TE) is often a barrier for early assessments. We aimed to investigate the diagnostic accuracy of serum indexes for predicting liver stiffness.

Retrospective analysis of HCV patients (with or without HIV coinfection) routinely assessed in 7 centres in Spain. The diagnostic accuracy of aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), and their combinations was evaluated using a recent TE examination as a reference test (liver stiffness ≥ 9.5 kPa and ≥12.5 kPa for advanced fibrosis and cirrhosis, respectively). In addition to area under the receiving operating characteristic curves, sensitivity, specificity, and negative predictive value (NPV) and positive predictive value were estimated.

The analysis included 1391 patients: 346 (25%) HIV-positive, 732 (53%) people who inject drugs, and 178 (13%) incarcerated. Advanced fibrosis and cirrhosis were found in 557 (40%) and 351 (25%) patients, respectively. APRI < 0.5 (n = 595; 43%) had an NPV of 95% for excluding cirrhosis. Combined FIB-4 < 1.45 with APRI < 0.5 (n = 467; 34%) had an NPV of 87% for excluding advanced fibrosis. Combined APRI > 2 and FIB-4 > 3.25 (n = 134; 10%) had a positive predictive value of 89% for advanced fibrosis. Globally, this approach would avoid the need for TE in 53% of patients. HIV coinfection did not influence diagnostic accuracy.

Inexpensive and simple serum indexes confidently allowed identifying the absence of cirrhosis and the presence of advanced fibrosis in 53% of a heterogeneous series of real-world HCV patients with or without HIV infection.