bluuebunny/crossref_metadata_2025 huggingface dataset:
The hepatoprotective potential of resveratrol in an experimental model of ruptured abdominal aortic aneurysm via oxidative stress and apoptosis
Authors: Bilen Arzu , Mercantepe Filiz , Tümkaya Levent , Yilmaz Adnan , Batcik Şule
Published: June 2021

The mortality rate in ruptured abdominal aortic aneurysms can today be reduced through cardiovascular surgery. However, ischemia and reperfusion‐induced tissue damage develop due to aortic cross‐clamping applied during surgery. The present study aimed to reduce oxidative stress‐induced hepatic damage resulting from ischemia and reperfusion due to aortic cross‐clamping during surgery by means of resveratrol administration. Forty male Sprague–Dawley rats were randomly assigned into four groups: control (healthy), glycerol+ischemia/reperfusion (I/R) (sham), I/R, and I/R + Resveratrol. In all groups scheduled for I/R, 60 min of shock was followed by 60 min of ischemia. In the I/R + Resveratrol group, 10 mg/kg of resveratrol was administered 15 min before ischemia and immediately before reperfusion via the intraperitoneal route. In addition, 120 min of reperfusion was applied under anesthesia after ischemia in all groups. Intralobar and interlobar necrosis, vascular congestion, and edematous fields resulting from aortic occlusion were present. Liver tissue malondialdehyde (MDA) levels and cleaved caspase‐3 positivity increased, while glutathione (GSH) levels decreased. However, resveratrol administration reduced intralobular and interlobar necrosis, vascular congestion and edematous fields, cleaved caspase‐3 positivity, and MDA levels, and increased GSH levels. Our findings suggest that resveratrol is effective against aortic occlusion‐induced liver injury by reducing oxidative stress and apoptosis.
Resident and house manager perceptions of social environments in sober living houses: Associations with length of stay
Authors: Mahoney Elizabeth , Witbrodt Jane , Mericle Amy A. , Polcin Douglas L.
Published: June 2021

Aims

Studies have shown persons living in recovery homes for drug and alcohol problems make significant, sustained improvements. However, there is limited information about factors associated with outcomes. This study examined how perceptions of social environment of one type of recovery home, sober living houses (SLHs), were associated with length of stay (LOS).

Methods

SLH residents and their house managers (N = 416) completed the recovery home environment scale (RHES) that assessed social model recovery characteristics and the community‐oriented program evaluation scale (CPES) that evaluated perceptions of the program environment.

Results

Scales completed by residents predicted LOS, but those completed by house managers did not. Larger discrepancies between the two groups were associated with shorter LOS. The RHES was shown to be a stronger predictor of LOS than the CPES.

Conclusion

Results highlight the importance of the social environment in SLHs, particularly those most closely aligned with social model recovery principles.
Foreign adolescents living in Portugal: Quality of life and school experiences
Authors: Botelho Guedes Fábio , Cerqueira Ana , Gaspar Susana , Gaspar Tania , Calado Pedro , Gaspar de Matos Margarida
Published: June 2021

The present study intends to (1) analyze the differences regarding the quality of life between young foreigners and young Portuguese adolescents; (2) understand the relationship between variables related to the school context and the quality of life of foreign adolescents living in Portugal. In all, 8215 adolescents participated in this study, and only the sub‐sample of 578 foreigners was considered. 50.3% are boys, aged between 10 and 22 years old. Foreign students in Portugal have a lower well‐being index than Portuguese students and a worse relationship with peers and teachers. Foreign girls like school more than boys, have less difficulties in school and have a higher perception of security at this context. On the other hand, they have a lower perceived academic competence and a worse relationship with peers. The importance of developing programs to promote socioemotional skills, empowering teachers and educators, and promoting the adoption of an inclusive model in schools is highlighted.
DL‐3‐n‐butylphthalide‐induced neuroprotection in rat models of asphyxia‐induced cardiac arrest followed by cardiopulmonary resuscitation
Authors: Yang Song , Yu Changxiao , Yang Zhengfei , Cui Hao , Wu Yang , Liang Zhen , Liu Ying , Shi Xian , Shao Fei , Zhao Shen , Tang Ziren
Published: June 2021

Most patients that resuscitate successfully from cardiac arrest (CA) suffer from poor neurological prognosis. DL‐3‐n‐butylphthalide (NBP) is known to have neuroprotective effects via multiple mechanisms. This study aimed to investigate whether NBP can decrease neurological impairment after CA. We studied the protective role of NBP in the hippocampus of a rat model of cardiac arrest induced by asphyxia. Thirty‐nine rats were divided randomly into sham, control, and NBP groups. Rats in control and NBP groups underwent cardiopulmonary resuscitation (CPR) 6 min after asphyxia. NBP or vehicle (saline) was administered intravenously 10 min after the return of spontaneous circulation (ROSC). Ultrastructure of hippocampal neurons was observed under transmission electron microscope. NBP treatment improved neurological function up to 72 h after CA. The ultrastructural lesion in mitochondria recovered in the NBP‐treated CA model. In conclusion, our study demonstrated multiple therapeutic benefits of NBP after CA.
Cerebellar spongiform degeneration is accompanied by metabolic, cellular, and motor disruption in male rats with portacaval anastomosis
Authors: López‐Cervantes Mayra , Quintanar‐Stephano Andrés , Alcauter‐Solórzano Sarael , Hernández‐Pando Rogelio , Aguilar‐Roblero Raúl , Gasca‐Martínez Deisy , Ortíz Juan J. , Vázquez‐Martínez Olivia , Ximénez‐Camilli Cecilia , Díaz‐Muñoz Mauricio
Published: June 2021

The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin‐4 and N‐acetylaspartate and a reduction in taurine and choline‐derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi‐disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.
Racial disparities in provider recommendation for esophagectomy for esophageal carcinoma
Authors: Merritt Robert E. , Abdel‐Rasoul Mahmoud , D'Souza Desmond M. , Kneuertz Peter J.
Published: June 2021

Background

Racial disparities currently exist for the utilization rate of esophagectomy for Black patients with operable esophageal carcinoma.

Methods

A total of 37 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Database were analyzed between 2004 and 2016. A multivariable‐adjusted logistic regression model was used to evaluate differences in the odds ratio of esophagectomy not being recommended based on race. Kaplan–Meier curves and log‐rank tests were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting (IPTW) was used to balance baseline differences in patient demographics.

Results

After IPTW adjustment, we identified 30 552 White patients and 3529 Black patients with clinical stage I–III esophageal carcinoma. Black patients had three times greater odds of not being recommended for esophagectomy (odds ratio: 3.03, 95% confidence interval: 2.67–3.43, p < 0.0001) compared to White patients. Black patients demonstrated significantly worse 3‐ and 5‐year overall survival rates compared to White patients (log‐rank p < 0.0001).

Conclusion

Black patients with clinical stage I–III esophageal cancer were significantly less likely to be recommended for esophagectomy even after adjusting for baseline demographic covariates compared to White patients.
Hiding in plain sight: The secret contribution of the solitary ascidian Herdmania grandis to temperate reef nitrous oxide production
Authors: Kelly Katie M. , Carlson‐Perret Natasha L. , Glaze Thomas D. , Erler Dirk V.
Published: June 2021

Large solitary ascidians, like Herdmania grandis (Heller), can dominate the benthic substrates of subtropical and temperate reefs; however, their influence on nitrogen cycling, particularly nitrous oxide (N2O) production, is unknown. Here, we incubated individual H. grandis and compared fluxes of dissolved inorganic and gaseous nitrogen species to fluxes from reef sediments. Nitrous oxide production rates per individual ascidian (21 ± 8 nmol ind h−1) are the highest reported for any marine invertebrate. An individual ascidian produced more N2O than 1 m2 of inter‐reef sediment (1.7 ± 1.7 nmol m−2 h−1). Ascidian mediated N2O production was found to occur under nutrient depleted conditions. The addition of 15N labeled organic material showed that the microbiota associated with H. grandis is capable of both nitrification and denitrification, but the contribution of these pathways to N2O production could not be ascertained. As the ecology of temperate reefs change, any range expansion of H. grandis will increase coastal N2O production.
CMTM4 regulates epithelial–mesenchymal transition and PD‐L1 expression in head and neck squamous cell carcinoma
Authors: Li Hao , Liu Yuan‐Tong , Chen Lei , Zhou Jun‐Jie , Chen De‐Run , Li Shu‐Jin , Sun Zhi‐Jun
Published: June 2021

The epithelial–mesenchymal transition (EMT) is a pivotal step involved in cancer recurrence and metastasis. In addition, the activation of the EMT program can induce a cancer stem cell (CSC)‐like phenotype and programmed death‐ligand 1 (PD‐L1) expression in head and neck squamous cell carcinoma (HNSCC). The CMTM family has reported as an important regulator in this process. Here, we investigated the role of CMTM4 in HNSCC. We indicated that CMTM4 was overexpressed in human and mouse HNSCC samples and in HNSCC cell lines by immunohistochemistry and Western blot. A high expression level of CMTM4 was correlated with advanced lymph node metastasis and a negative prognosis. CMTM4‐knockdown by small interfering RNA downregulated the EMT process and inhibited the migration and invasion abilities of tumor cells. Moreover, knockdown of CMTM4 decreased CSC‐associated markers via the protein kinase B pathway. Notably, CMTM4‐knockdown inhibited the expression of interferon‐γ induced PD‐L1 in HNSCC cells. A positive correlation was found between CMTM4 expression and CD8+ and PD‐1+ cell density in the stroma. Our findings indicated that CMTM4 may play an important role in regulating EMT/CSC phenotypes and PD‐L1 expression. This study may reinforce the interest in CMTM4 as a potential target for the prognosis and treatment of HNSCC.
Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome
Authors: Friedman Jennifer , Bird Lynne M. , Haas Richard , Robbins Shira L. , Nahas Shareef A. , Dimmock David P. , Yousefzadeh Matthew J. , Witt Mariah A. , Niedernhofer Laura J. , Chowdhury Shimul
Published: June 2021

Background

Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. Excision repair cross‐complementation group 6 (ERCC6 OMIM: *609413) is the gene most frequently mutated in CS.

Methods

A child with pre and postnatal growth failure and progressive neurologic deterioration with multisystem involvement, and with nondiagnostic whole‐exome sequencing, was screened for causal variants with whole‐genome sequencing (WGS).

Results

WGS identified biallelic ERCC6 variants, including a previously unreported intronic variant. Pathogenicity of these variants was established by demonstrating reduced levels of ERCC6 mRNA and protein expression, normal unscheduled DNA synthesis, and impaired recovery of RNA synthesis in patient fibroblasts following UV‐irradiation.

Conclusion

The study confirms the pathogenicity of a previously undescribed upstream intronic variant, highlighting the power of genome sequencing to identify noncoding variants. In addition, this report provides evidence for the utility of a combination approach of genome sequencing plus functional studies to provide diagnosis in a child for whom a lengthy diagnostic odyssey, including exome sequencing, was previously unrevealing.
An extended superficial circumflex iliac artery perforator flap transfer for a relatively‐small breast reconstruction after total mastectomy
Authors: Yamamoto Takumi , Yamamoto Nana
Published: June 2021

Superficial circumflex iliac artery (SCIA) perforator (SCIP) flap has been applied in various reconstructions. Unlike traditional groin flap, SCIP flap has a longer pedicle and can be used as a chimeric flap for complex reconstruction. By utilizing both the superficial and the deep branches of the SCIA, a SCIP flap can be raised as an extended large bulky flap. Although there are many articles reporting usefulness of SCIP flap, there is no case reporting a large SCIP flap transfer for breast reconstruction after total mastectomy. We applied a free extended SCIP flap for a case of post‐total‐mastectomy breast reconstruction. A 51‐year‐old female who had undergone total mastectomy and sentinel lymph node biopsy was referred for autologous tissue breast reconstruction. Physical exam revealed that the iliac and lower abdominal regions were suitable for a donor site. As the patient desired to preserve a similar donor site for possible future contralateral breast reconstruction, the iliac region was selected as a donor site. A 23 × 15 cm SCIP flap was elevated based on the superficial and the deep branches of the SCIA, and was transferred to the recipient site. The SCIA and concomitant vein were anastomosed to the lateral thoracic artery and vein in an end‐to‐end fashion. Postoperative course was uneventful. The reconstructed breast shape and texture were similar to the contralateral breast with no donor site complication, and the patient was very satisfied with functionally and esthetically pleasing results. Extended SCIP flap may be an option for relatively‐small breast reconstruction.
Diosgenin Protects Against Kidney Injury and Mitochondrial Apoptosis Induced by 3‐MCPD Through the Regulation of ER Stress, Ca2+ Homeostasis, and Bcl2 Expression
Authors: Zhong Yujie , Jin Chengni , Han Jiahui , Zhu Jiachang , Liu Qi , Sun Dianjun , Xia Xiaodong , Zhang Yu , Peng Xiaoli
Published: June 2021

Scope

Diosgenin (DIO) is a natural steroid sapogenin presented in various plants. It exerts anti‐oxidant, anti‐inflammatory and anti‐diabetic nephropathy properties. The present study evaluates the intervention effect of DIO on nephrotoxicity induced by food contaminant 3‐chloro‐1, 2‐propanediol (3‐MCPD) in vivo and in vitro.

Methods and Results

Treatment with DIO (15 mg kg−1 d−1) in Sprague‐Dawley rats for 4‐week relieves kidney injury induced by 3‐MCPD (30 mg kg−1 d−1). In vitro, DIO (2, 6, and 8 µM) alleviates cell injury and apoptosis effectively in human embryonic kidney (HEK293) cells. DIO realizes its protective function via the regulation of endoplasmic reticulum (ER) stress and mitochondrial apoptosis pathway. Blockage of ER stress by 4‐phenylbutyric acid (4‐PBA), a specific ER stress antagonist, inhibits mitochondrial apoptosis, suggesting a connection between mitochondrial apoptosis and ER stress. Furthermore, the study demonstrates that the maintenance of Ca2+ homeostasis and Bcl2 expression, two main targets of ER stress, contributes to the protection role of DIO on mitochondrial‐dependent apoptosis. In addition, DIO relieves the impairment of oxidative phosphorylation.

Conclusion

This study demonstrates that DIO exerts protective effect against kidney injury, mitochondrial dysfunction, and apoptosis through the inhibition of ER stress and the further maintenance of Ca2+ homeostasis and Bcl2 expression.
Glutaminolysis is involved in the activation of mTORC1 in in vitro‐produced porcine embryos
Authors: Chen Paula R. , Lucas Caroline G. , Spate Lee D. , Prather Randall S.
Published: June 2021

Glutamine supplementation to porcine embryo culture medium improves development, increases leucine consumption, and enhances mitochondrial activity. In cancer cells, glutamine has been implicated in the activation of mechanistic target of rapamycin complex 1 (mTORC1) to support rapid proliferation. The objective of this study was to determine if glutamine metabolism, known as glutaminolysis, was involved in mTORC1 activation in porcine embryos. Culture with 3.75 mM GlutaMAX improved development to the blastocyst stage compared to culture with 1 mM GlutaMAX, and culture with 0 mM GlutaMAX decreased development compared to all groups with GlutaMAX. Ratios of phosphorylated to total MTOR were increased when embryos were cultured with 3.75 or 10 mM GlutaMAX, which was enhanced by the absence of leucine, but ratios for RPS6K were unchanged. As another indicator of mTORC1 activation, colocalization of MTOR and a lysosomal marker was increased in embryos cultured with 3.75 or 10 mM GlutaMAX in the absence of leucine. Culturing embryos with glutaminase inhibitors decreased development and the ratio of phosphorylated to total MTOR, indicating reduced activation of the complex. Therefore, glutaminolysis is involved in the activation of mTORC1 in porcine embryos, but further studies are needed to characterize downstream effects on development.
Synthesis, characterization, and adsorption properties of collagen and attapulgite‐filled copolymer biocomposites: Batch and column studies
Authors: Choudhury Swastika , Ray Samit Kumar
Published: June 2021

Several biocomposites were synthesized by copolymerizing hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) at varied molar ratios in the presence of different wt% of collagen (CLG) and attapulgite (APG) clay. The structure and properties of the biocomposite adsorbents were characterized by Fourier transform infrared apectroscopy, nuclear magnetic resonance, X‐ray photo electron spectroscopy, X‐ray diffraction, scanning electron microscope, transfer electron microscopy, energy‐dispersive X‐ray analysis, differential thermal analysis–thermogravimetric analysis, point zero charge analysis, mechanical properties, and pH reversibility tests. The synthesis variables were optimized with a central composite design of response surface methodology (RSM). The biocomposite prepared with an optimized composition of 1.5 wt% CLG, 1.7 wt% APG, and 5:1 molar ratio of HEMA:IA showed an adsorption capacity (Qe, mg/g) of 674.4/602.4 for methylene blue (MB)/Rose Bengal (RB) dye from a feed containing 200 mg/L of MB + RB dye mixture in batch mode. In a fixed bed in column mode, the optimized biocomposite showed a removal% of 82.8/71.3 for 100 mg/L inlet concentration, 20 ml/min flow rate, and 20 mm bed height with a breakthrough time of 23/31 min and a mass transfer coefficient (kmtc × 105 cm/s) of 8.36/7.67 for MB/RB as single dye solution.
Synthesis of Polyetheramine Based Bonding Agents and Their Effect on Mechanical Properties of an AP/CL‐20/GAP Formulation
Authors: Xu Shuang , Pang Ai‐Min , Wu Zhuo , Li Hai‐Tao , Li Wei , Kong Jie
Published: June 2021

Two types of bonding agents were synthesized based on polyetheramines (PEAs), which aim to increase the strain of AP/CL‐20/GAP formulation. The PEAs, terminated with cyano (CTPEA) and Schiff base (SBPEA) groups, were applied in the AP/CL‐20/GAP formulation, respectively. The results showed that the bonding agents TCN‐403 (CTPEA) and TBA‐403 (SBPEA), which were prepared from trifunctional PEA named as T‐403, could significantly increase the maximum elongation ratio of the formulation. The differences between the TCN‐403 and TBA‐403 were analyzed by DMA of the formulations, SEM of the coated fillers, and in‐situ tensile test, indicating that the Schiff base bonding agents can effectively inhibit the dewetting of the binder from the solid particles in the formulations.
A computational framework for modeling functional protein‐protein interactions
Authors: Pal Abantika , Pal Debnath , Mitra Pralay
Published: June 2021

Protein interactions and their assemblies assist in understanding the cellular mechanisms through the knowledge of interactome. Despite recent advances, a vast number of interacting protein complexes is not annotated by three‐dimensional structures. Therefore, a computational framework is a suitable alternative to fill the large gap between identified interactions and the interactions with known structures. In this work, we develop an automated computational framework for modeling functionally related protein‐complex structures utilizing GO‐based semantic similarity technique and co‐evolutionary information of the interaction sites. The framework can consider protein sequence and structure information as input and employ both rigid‐body docking and template‐based modeling exploiting the existing structural templates and sequence homology information from the PDB. Our framework combines geometric as well as physicochemical features for re‐ranking the docking decoys. The proposed framework has an 83% success rate when tested on a benchmark dataset while considering Top1 models for template‐based modeling and Top10 models for the docking pipeline. We believe that our computational framework can be used for any pair of proteins with higher confidence to identify the functional protein‐protein interactions.
Interfacial Magnetic Behaviors and Chemical States of Fe Grown on MoS2
Authors: Tuli Farhana Jesmin , Kibria Mohammad Tawheed , Nakagawa Takeshi , Mizuno Seigi
Published: June 2021

Magnetic and chemical properties of ultrathin Fe films on molybdenum disulfide (MoS2) are investigated using magneto‐optic Kerr effect (MOKE) and X‐ray photoemission spectroscopy (XPS). A magnetization hysteresis loop is found after nominal 10 Å of Fe deposition on MoS2 at room temperature. The thickness‐dependent MOKE measurement evaluates that the magnetic dead layer (MDL) exists up to ≈2 Å of Fe on MoS2 due to the interaction between Fe and MoS2. XPS shows small peak shifting for Mo 3d and S 2p peaks toward lower binding energies with initial Fe deposition, indicating the modification of surface band bending. Fe 2p peaks for lower thickness of Fe are significantly broader than those for higher thickness, which is attributed to the coexistence of metallic and ionic Fe in the film. The presence of ionic Fe, localized at the interface, indicates strong interactions between Fe and MoS2, and the existence of chemical bonding at the interface is corroborated with the formation of MDL.
Functional recovery from eccentric injury is maintained in sarcopenic mouse muscle
Authors: Valencia Ana P. , Samuelson Ashton T. , Stuppard Rudolph , Marcinek David J.
Published: June 2021

Background

Eccentric contractions induce muscle damage (EIMD) that compromises muscle function. Poor recovery from EIMD has been suggested to be a contributor to the decline in muscle function evident in sarcopenia, but it is unclear which aspects of muscle function are more susceptible to disruption by EIMD in old versus young muscle. The purpose of this study was to determine the extent of impairment in contractile function (force, fatigue, tetanus and twitch kinetics) during the recovery from EIMD in VO mice compared to young adult (YA).

Methods

Male CB6F1 were obtained from National Institure of Aging colony. VO mice were 29–31 months of age, and YA mice were 7–9 months of age. The plantarflexor muscles were subjected to 20 eccentric contractions in vivo to induce injury (EIMD). Changes in tetanic force and kinetics were assessed before EIMD, immediately after EIMD and 3 days after EIMD (3d‐EIMD). Force–frequency and rates of fatigue were assessed 3d‐EIMD and compared with baseline. Histological analysis was conducted in injured and non‐injured contralateral gastrocnemius muscle.

Results

There was a greater loss in isometric tetanic force immediately following EIMD in VO compared with YA (−31.6% ± 10.4 vs. −21.7% ± 6.0, P < 0.05). At 3d‐EIMD, the rate of contraction of tetanus began to recover in VO, but not in YA (20.8% vs. −6.8%, P < 0.05), whereas the extent of recovery of force tended to be greater in VO than YA (39.3% vs. 17.1%, P = 0.08) when compared with tetanic function immediately after injury. Compared with function pre‐injury (baseline), VO and YA had similar deficits in tetanic force (−7.3% ± 5.3 vs. ‐9.2% ± 6.0, respectively) and kinetics at Day 3. Twitch kinetics (rate of relaxation) recovered faster in VO compared with YA. The rate of muscle fatigue was similar to baseline values, with VO continuing to be more fatigue resistant than YA 3d‐EIMD. There were no detectable differences in muscle mass or myofibre cross‐sectional area despite continued deficits in force following EIMD in either age group.

Conclusions

Despite clear functional deficits and greater susceptibility to injury, aged sarcopenic muscle exhibited a similar ability to recover contractile function to younger muscle following EIMD. In addition, neither age group showed accelerated muscle fatigue in the recovery phase after EIMD; thus, sarcopenic mouse muscles do not appear to be more susceptible to long‐term functional impairment than young healthy muscles.
Suboptimal reduced control of unknown nonlinear singularly perturbed systems via reinforcement learning
Authors: Liu Xiaomin , Yang Chunyu , Zhou Linna , Fu Jun , Dai Wei
Published: June 2021

In this paper, a suboptimal reduced control method is proposed for a class of nonlinear singularly perturbed systems (SPSs) with unknown dynamics. By using singular perturbation theory, the original system is reduced to a reduced system, by which a policy iterative method is proposed to solve the corresponding reduced Hamilton–Jacobi–Bellman (HJB) equation with convergence guaranteed. A reinforcement learning (RL) algorithm is proposed to implement the policy iterative method without using any knowledge of the system dynamics. In the RL algorithm, the unmeasurable state of the virtual reduced system is reconstructed by the slow state measurements of the original system, the controller and cost function are approximated by actor‐critic neural networks (NNs) and the method of weighted residuals is utilized to update the NN weights. The influence introduced by state reconstruction error and NN function approximation on the convergence, suboptimality of the reduced controller and stability of the closed‐loop SPSs are rigorously analyzed. Finally, the effectiveness of our proposed method is illustrated by examples.
Borylation and Stannylation Reactions with Tuning of Lewis Acidity
Authors: Yoshida Hiroto
Published: June 2021

A B(dan) moiety (dan=naphthalene‐1,8‐diaminato) of diminished boron‐Lewis acidity has efficiently been installed into organic frameworks by three‐component carboboration of alkenes under copper catalysis, where a Cu−B(dan) species, generated by chemoselective σ‐bond metathesis between a copper catalyst and an unsymmetrical diboron [(pin)B−B(dan)], acts as a key intermediate. The Cu−B(dan) species has also turned out to serve as a B(dan) nucleophile to afford various dan‐substituted organoboranes via borylative substitution of carbon electrophiles. Furthermore, borylation reactions with another Lewis acidity‐diminished boron unit, B(aam) (aam=anthranilamidato), have become feasible by use of (pin)B−B(aam) or H−B(aam). The resulting dan/aam‐substituted organoboranes have been demonstrated to undergo direct cross‐coupling without prior acidic deprotection, regardless of their diminished boron‐Lewis acidity. Synthesis of diverse organostannanes based upon copper‐catalyzed carbostannylation and borylstannylation, in which Lewis acidity increment of a tin center facilitates the progress in some cases, have also been described.
Cycloisomerization of π‐Coupled Heteroatom Nucleophiles by Gold Catalysis: En Route to Regiochemically Defined Heterocycles
Authors: Praveen Chandrasekar
Published: June 2021

Since the dawn of millennium, catalytic gold chemistry is at the forefront to set off diverse organic reactions via unique activation of π‐bonded molecules. Within this purview, cycloisomerization of heteroatom nucleophiles linked to a π‐system is one of the well recognized chemistry for the construction of numerous heterocyclic cores. Though the rudimentary aspects of this transformation are reviewed by several groups in different timeline, a holistic view on regiochemistry of such reactions went largely overlooked. Hence, this account emphasizes the gold catalyzed regioselective cycloisomerization of structurally distinctive π‐connected hetero‐nucleophiles leading to different heterocycles documented in the last two decades. From an application perspective, this account also highlights those methodologies which find a role in the total synthesis of natural products. Wherever appropriate, mechanistic details and contributing factors for selectivity are also discussed.
Early risk stratification of patients with suspected chronic mesenteric ischaemia using a symptom and mesenteric artery calcium score based score chart
Authors: Terlouw Luke G. , van Noord Desirée , van Walsum Theo , van Dijk Louisa J. D. , Moelker Adriaan , Bruno Marco J.
Published: June 2021

Background

The mesenteric artery calcium score (MACS) identifies patients with possible chronic mesenteric ischaemia (CMI) using standard computed tomography (CT) imaging. The MACS does not necessitate a dedicated computed tomography angiography (CTA) which is required for evaluation of mesenteric artery patency. This study aimed to test the use of a symptom and MACS based score chart to facilitate the selection of patients with a low probability of CMI, in whom further diagnostic workup can be omitted, and to validate the CTA‐based score chart proposed by van Dijk et al. which guides treatment decisions in patients with suspected CMI.

Methods

This retrospective study included consecutive patients with suspected CMI. The Agatston definition was used to calculate the MACS. Multivariable logistic regression analysis was used to create a MACS score chart, which was applied in all patients to determine its discriminative ability. The score chart by van Dijk et al. was validated in this independent external patient series.

Results

Hundred‐ninety‐two patients were included, of whom 49 had CMI. The MACS score chart composed of the variables weight loss, postprandial abdominal pain, history of cardiovascular disease, and MACS, showed an excellent discriminative ability (area under the curve [AUC] 0.87). CMI risks were 2.1% in the low‐risk group (0–4 points) and 39.1% in the increased risk group (5–10 points); sensitivity (97.8%) and negative predictive value (NPV; 97.9%) were high. The CTA‐based score chart by van Dijk et al. showed an excellent discriminative ability (AUC 0.89).

Conclusion

The MACS score chart shows promise for early risk stratification of patients with suspected CMI based on a near‐perfect NPV. It is complementary to the CTA‐based score chart by van Dijk et al., which showed excellent external validity and is well suited to guide subsequent (invasive) treatment decisions in patients with suspected CMI.
Decreased inferior vena cava diameter as an early marker in postpartum hemorrhage
Authors: Massalha M. , Faranish R. , Romano S. , Salim R.
Published: June 2021

Objectives

To examine the association between inferior vena cava (IVC) diameter and postpartum blood loss and assess whether IVC diameter is a useful marker in the evaluation of intravascular volume status in women with postpartum hemorrhage (PPH).

Methods

This was a prospective case–control study conducted in a university medical teaching center in Afula, Israel, between November 2018 and March 2020. The study cohort consisted of women with a singleton pregnancy who delivered vaginally at term. The PPH group included women diagnosed with PPH based on visually estimated blood loss of 1000 mL or more at the time of enrolment. Hemodynamically unstable women or women with major bleeding at the time of diagnosis were not included. The control group consisted of women with an uneventful fourth stage of labor. IVC diameter was measured using transabdominal ultrasonography during inspiration (IVCi diameter) and expiration (IVCe diameter), and the collapsibility index was calculated ((IVCe – IVCi)/IVCe × 100). The primary outcome was the percentage difference in IVC diameter and collapsibility index between the PPH group and controls. The performance of the IVC collapsibility index in the prediction of the need for blood transfusion in women with PPH was assessed. In order to demonstrate a difference of 20% with a power of 80% and alpha of 0.05, 108 women, at a ratio of 1:2 in the study and control groups, respectively, were needed.

Results

Overall, 36 and 72 women were included in the final analysis in the PPH and control groups, respectively. IVCi and IVCe diameters were significantly smaller in the PPH group (0.93 ± 0.30 cm and 1.26 ± 0.32 cm, respectively) than in controls (1.42 ± 0.31 cm and 1.75 ± 0.28 cm, respectively) (P = 0.001 for both). The percentage reductions in IVCi and IVCe diameters in the PPH group compared with controls were 35.0% and 28.0%, respectively. IVC collapsibility index was increased significantly, by 42.9% (26.04 ± 8.67% vs 18.15 ± 5.07%; P = 0.001) in the PPH group compared with controls. IVC collapsibility index was a significant predictor of the need for blood transfusion and correctly predicted 81% of cases. Logistic regression analysis demonstrated that IVC collapsibility index was also a significant predictor of a drop in hemoglobin level of ≥ 2 g/dL (P = 0.001).

Conclusions

IVC diameter changes in response to postpartum blood loss. Measurement of IVC diameter using transabdominal ultrasonography is an objective and useful non‐invasive method for the early evaluation of intravascular volume status in women with PPH and for the prediction of cases that might require blood transfusion. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Where and when to Use Induction Chemotherapy in Head and Neck Squamous Cell Cancer
Authors: Vermorken Jan B.
Published: June 2021

The treatment of locoregionally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) is reviewed, highlighting the milestones in systemic therapy in that setting, with focus on the role of induction chemotherapy (ICT). The road to what is now considered the standard ICT regimen, i.e. the TPF (docetaxel/cisplatin/5-FU) regimen is described, and the differences between the European and the American TPF are discussed. The article describes the respective roles of ICT for larynx preservation, for treatment intensification, its role in patients with borderline resectable or unresectable oral cavity cancer, its role as a selection tool for radiotherapy dose de-escalation in patients with oropharyngeal squamous cell cancer (OPSCC) and its potential future role in strategies aiming at synchronous oligometastatic disease.

ICT has an established role for organ preservation in advanced laryngeal and hypopharyngeal cancer and the TPF regimen has been validated in that setting. This approach is presently being compared in a randomized controlled trial to concurrent chemoradiotherapy (CCRT), which in many parts of the world is considered the standard organ preservation procedure. There remains uncertainty about the benefit of the sequential approach of ICT followed by CCRT, despite the fact that ICT significantly reduces the occurrence of distant metastases. It is advised that future studies should include patients who have the highest risk to develop distant metastases, in particular patients with low neck nodes and matted nodes. Moreover, further studies in patients with HPV-associated OPSCC at risk for distant failure (T4 or N3 disease) should be considered for that also. These approaches still need to be confirmed in adequately sized randomized controlled trials. Outside clinical trials, the utility of ICT is restricted to uniquely pragmatic clinical scenarios, such as unavoidable delay in radiation or in the situation that RT is not tolerated or feasible. This can happen when there is severe pain from advanced disease or there is impending airway compromise or neurologic dysfunction that necessitates rapid initiation of treatment. In all those circumstances whether within the context of trials or outside trials, it is imperative that the present backbone of ICT, the TPF regimen, is being administered by experienced oncologists, familiar with the necessary protocols and supportive care requirements to ensure patient safety and maximize adherence throughout the treatment.

Future areas of research are the role of ICT in strategies whereby ICT is combined with upfront metastases-directed treatments and the usefulness of targeted agents or immune checkpoint inhibitors in the induction setting. Studies in that direction have already started. Finally, the application of radiographic, proteomic and genomic biomarkers will get attention to further define prognostic groups and guide treatment selection with greater precision.
Tracheostomy Practices for Mechanically Ventilated Patients in Malawi
Authors: Prin Meghan , Kaizer Alex , Cardenas Jesus , Mtalimanja Onias , Kadyaudzu Clement , Charles Anthony , Ginde Adit
Published: June 2021

Background

Tracheostomy is used for patients who require prolonged mechanical ventilation. Extensive research has described the provision and optimal timing of tracheostomy, but very little describes tracheostomy utilization in low‐ and middle‐income countries, particularly in sub‐Saharan Africa.

Methods

This prospective cohort study describes patients admitted to the intensive care unit (ICU) of a tertiary hospital in Malawi who received tracheostomy versus those who did not, with a primary outcome of hospital mortality. We performed subgroup analysis of patients with severe head injuries.

Results

The analysis included 451 patients admitted to the study ICU between September 2016 and July 2018. Overall hospital mortality was 40% for patients who received tracheostomy and 63% for patients who did not. Logistic regression modeling revealed an odds ratio (OR) of 0.34 (95% CI 0.18–0.64) for hospital mortality among patients who received tracheostomy versus those who did not (p < 0.001). Standardized mortality ratio weighting revealed an odds ratio of 0.81 (95% CI 0.65–0.99, p < 0.001) for hospital death among patients who received tracheostomy versus those who did not. In the subgroup excluding severe head injury, both ICU (50%) and hospital mortality (75%) were higher overall, but hospital mortality was not more common for patients with tracheostomy versus without (OR 1.28, 95% CI 0.94–1.74, p = 0.104).

Conclusions

Tracheostomy is not associated with hospital mortality in a Malawi ICU cohort, but these results are affected by the presence of head injury. Research may focus on home tracheostomy care given the lack of hospital discharge options for patients in austere settings.
68Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial
Authors: Bowden Patrick , See Andrew W. , So Kevin , Lawrentschuk Nathan , Moon Daniel , Murphy Declan G. , Rao Ranjit , Crosthwaite Alan , King Dennis , Haxhimolla Hodo , Grummet Jeremy , Ruljancich Paul , Gyomber Dennis , Landau Adam , Campbell Nicholas , Frydenberg Mark , Smyth Lloyd M. L. , Nolan Skye , Gwini Stella M. , McKenzie Dean P.
Published: June 2021

Purpose

To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET).

Methods

This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL).

Results

Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable.

Conclusion

Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL.

Trial registration number

ACTRN12615001183572, 03/11/2015, retrospectively registered.
Independent Sets in ($$P_4+P_4$$,Triangle)-Free Graphs
Authors: Mosca Raffaele
Published: June 2021

The Maximum Weight Independent Set Problem (WIS) is a well-known NP-hard problem. A popular way to study WIS is to detect graph classes for which WIS can be solved in polynomial time, with particular reference to hereditary graph classes, i.e., defined by a hereditary graph property or equivalently by forbidding one or more induced subgraphs. Given two graphs G and H, $$G+H$$

G
+
H

denotes the disjoint union of G and H. This manuscript shows that (i) WIS can be solved for ($$P_4+P_4$$

P
4

+

P
4

, Triangle)-free graphs in polynomial time, where a $$P_4$$

P
4

is an induced path of four vertices and a Triangle is a cycle of three vertices, and that in particular it turns out that (ii) for every ($$P_4+P_4$$

P
4

+

P
4

, Triangle)-free graph G there is a family $${{\mathcal {S}}}$$
S
of subsets of V(G) inducing (complete) bipartite subgraphs of G, which contains polynomially many members and can be computed in polynomial time, such that every maximal independent set of G is contained in some member of $${\mathcal {S}}$$
S
. These results seem to be harmonic with respect to other polynomial results for WIS on [subclasses of] certain $$S_{i,j,k}$$

S

i
,
j
,
k

-free graphs and to other structure results on [subclasses of] Triangle-free graphs.
Skin diseases in hospitalized geriatrics: a 9-year analysis from a University Dermatology Center in Germany
Authors: Ansorge Claudia , Miocic Johannes M. , Schauer Franziska
Published: June 2021

The demographic trend of an ageing society is mirrored in the rising number of hospitalized geriatric patients in Germany. However, there is still a wide gap of knowledge regarding the dermatological diseases, comorbidities and performed procedures within this growingly important group of patients. The study was conducted as a retrospective monocentric data analysis of all patients 65 years or older from the Department of Dermatology, Medical Center—University of Freiburg, Germany. In total, 10,009 individual hospitalisations were included from 2009 to 2017, and there was a notable increase of geriatric patients in the study period. This study illustrates the following: leading major diagnoses included malignant neoplasm of the head and neck, ulcerated and non-ulcerated inflammatory spectrum of chronic venous insufficiency, whereas angina pectoris, type 2 diabetes and cardiac diseases were noted most frequently as secondary diagnoses. Patients with venous diseases had considerably more often cardiopulmonary minor diagnoses, whereas endocrine diagnoses peaked in the cohort of patients with psoriasis and psychiatric and muscululoskeletal disorders in patients with bullous dieseases. Moh’s surgery, dressings and multimodal dermatological treatments were the most often encoded procedures.
Workplace bullying increases the risk of anxiety through a stress-induced β2-adrenergic receptor mechanism: a multisource study employing an animal model, cell culture experiments and human data
Authors: Rajalingam Dhaksshaginy , Nymoen Ingeborg , Nyberg Henriette , Nielsen Morten Birkeland , Einarsen Ståle Valvatne , Gjerstad Johannes
Published: June 2021

Objectives

Several studies show that severe social stressors, e.g., in the form of exposure to workplace bullying in humans, is associated with negative mental health effects such as depression and anxiety among those targeted. However, the understanding of the underlying biological mechanisms that may explain the relationship between exposure to bullying and such negative health outcomes is scarce. The analyses presented here focus on understanding the role of the β2-adrenergic receptors (ADRB2) on this association.

Methods

First, a resident-intruder paradigm was used to investigate changes in circulating norepinephrine (NE) in rat serum induced by repeated social defeat and its relationship with subsequent social behavior. Second, the direct effects of the stress-hormones NE and cortisol, i.e., synthetic dexamethasone (DEX), on the ADRB2 expression (qPCR) and monocyte chemoattractant protein-1 (MCP-1) release (immunoassay) was examined in cultured EL-1 cells. Third, in a probability sample of 1052 Norwegian employees, the 9-item short version of the Negative Acts Questionnaire—Revised (S-NAQ) inventory, Hopkins Symptom Checklist and genotyping (SNP TaqMan assay) were used to examine the association between social stress in the form of workplace bullying and anxiety moderated by the ADRB2 genotype (rs1042714) in humans.

Results

The present study showed a clear association between reduced social interaction and increased level of circulating NE in rats previously exposed to repeated social defeat. Parallel cell culture work, which was performed to examine the direct effects of NE and DEX on ADRB2, demonstrated ADRB2 downregulation and MCP-1 upregulation in cultured EL-1 cells. Genotyping with regard to the ADRB2 genotype; rs1042714 CC vs CG/GG, on human saliva samples, showed that individuals with CC reported more anxiety following exposure to bullying behaviors as compared to the G carriers.

Conclusion

We conclude that workplace bullying promotes anxiety and threaten well-being through an ADRB2 associated mechanism.