bluuebunny/crossref_metadata_2025 huggingface dataset:
The Justice Department's Pattern-or-Practice Police Reform Program, 1994–2017: Goals, Achievements, and Issues
Authors: Walker Samuel
Published: August 2021

The Department of Justice's pattern-or-practice police reform program has been an unprecedented event in American policing, intervening in local and state law enforcement agencies as never before and requiring a sweeping package of reforms. The program has reached reform settlements with forty agencies, including twenty with judicially enforced consent decrees. Academic research on the program, however, has been fairly modest. Social scientists have largely focused on a few selected issues. There is no study of the full impact of the program on one agency, and there is no comprehensive study of the impact of the program as a whole. Evaluations of individual agencies have been generally favorable, although with backsliding in some agencies. This review argues that the combination of several major goals and the various elements of specific consent decree reforms has created a web of accountability that is unmatched by any previous police reform effort.
Anxiogenic Potential of Experimental Sleep Fragmentation Is Duration‐Dependent and Mediated via Oxidative Stress State
Authors: Grubač Željko , Šutulović Nikola , Šuvakov Sonja , Jerotić Djurdja , Puškaš Nela , Macut Djuro , Rašić-Marković Aleksandra , Simić Tatjana , Stanojlović Olivera , Hrnčić Dragan
Published: August 2021

Sleep architecture alterations, among which sleep fragmentation is highly prevalent, represent risk factors for a variety of diseases, ranging from cardiovascular to brain disorders, including anxiety. What mediates anxiety occurrence upon sleep fragmentation is still a matter of debate. We hypothesized that the sleep fragmentation effects on anxiety are dependent on its duration and mediated by increased oxidative stress and alterations in the number of parvalbumin (PV+) interneurons in the hippocampus. Sleep was fragmented in rats by the treadmill method during a period of 14 days (SF group). Rats with undisturbed sleep in the treadmill (TC group) and those receiving equal amounts of treadmill belt motion (EC group) served as controls. To assess anxiety, we subjected rats to the open field, elevated plus maze, and light‐dark tests on the 0, 7th, and 14th day. Upon the last test, brain structures were sampled for oxidative stress assessment and PV+ interneuron immunohistochemistry. The results of ethological tests of anxiety‐linked behavior suggested duration‐dependent anxiogenic potential of sleep fragmentation. Rats’ anxiety‐linked behavior upon sleep fragmentation significantly correlated with oxidative stress. The rats with fragmented sleep (SF) showed significantly higher oxidative stress in the hippocampus, thalamus, and cortex, compared to controls (TC and EC), while the antioxidant enzymes’ activity was significantly decreased. No significant differences were observed in hippocampal PV+ interneurons among these groups. Our results showed that duration of sleep fragmentation is a significant determinant of anxiety‐linked behavior, and these effects are mediated through oxidative distress in the brain. Herein, it is revealed that the sleep fragmentation‐oxidative stress‐anxiety axis contributes to our better understanding of pathophysiological processes, occurring due to disrupted sleep patterns.
Influence of Four Ageing Methods on the Mechanical Properties of Bamboo Scrimber
Authors: Wang Hongyan , Yuan Shaofei , Zhang Jian , Li Qin
Published: August 2021

In this study, the six-cycle accelerated ageing method (method I), the 6 h boiling-freezing-drying method (method II), the wet circulation method (method III), and the boiling-testing method (method IV), which are accelerated ageing testing methods, were used to study the ageing resistance of bamboo scrimber. Changes in the nail-holding power of the plane, the side, and the end face of untreated/treated bamboo scrimber were analyzed systematically, including other changes in mechanical properties, such as the horizontal shear strength, the modulus of rupture (MOR), and the modulus of elasticity (MOE) along the smooth grain, etc. The results show that all mechanical properties decreased after treatment with the four accelerated ageing testing methods: the nail-holding power decreased by 4%~42% on the plane, 8%~40% on the side, and 5%~66% on the end face. The horizontal shear strength decreased by 3.1%~16.7%, the MOR decreased by 15%~27.2%, and the MOE decreased by 2.6%~12.8%. The nail-holding power of the three sides and the MOR were the most affected properties after treatment. So, the nail-holding power and the MOR can be chosen as important indices to evaluate bamboo scrimber’s weather resistance. For the four accelerated ageing testing methods, the degree of influence on the nail-holding power was in this sequence: method I > method III > method IV > method II. However, after comprehensive consideration, the degree of influence on the mechanical properties was in this sequence: method I > method IV > method III > method II.
The Connections between Attitudes towards Nursing Home Placement, Intergenerational Solidarity, and the Conflict between Tradition and Modernity among Three Generations of Arab Muslim Families in Israel
Authors: Ron Pnina
Published: August 2021

The goal of this study was to examine three generations of Arab Muslims in Israel, to investigate the relationships between their attitudes regarding the placement of an older relative in a nursing home, intergenerational solidarity, and to ultimately proceed with the nursing home placement. The backdrop to this examination was the increasing sociocultural tension between modernization tendencies and the long-established traditions and norms in the Arab Muslim society in Israel. The sample included a total of 126 university students, as well as one parent and one grandparent of each student. All participants completed identical questionnaires examining the attitudes towards the nursing home placement of an elder relative. The findings of the study indicate a strong objection among the youngest generation, whose attitudes were more similar to those of their grandparents than to those of their parents. Psychosocial mechanisms in the Arab Muslim population, such as intergenerational solidarity, has been the subject of increased scrutiny and debate over recent years, given the intensive pace of modern developments, which has called into question the familiar norms, thus constituting a threat to the tradition that has guided the population throughout numerous centuries and generations.
Investigation of General Power Sum‐Connectivity Index for Some Classes of Extremal Graphs
Authors: Cheng Rui , Ali Gohar , Rahmat Gul , Khan Muhammad Yasin , Semanicova-Fenovcikova Andrea , Liu Jia-Bao
Published: August 2021

In this work, we introduce a new topological index called a general power sum‐connectivity index and we discuss this graph invariant for some classes of extremal graphs. This index is defined by , where d(u) and d(v) represent the degree of vertices u and v, respectively, and α ≥ 1. A connected graph G is called a k‐generalized quasi‐tree if there exists a subset Vk ⊂ V(G) of cardinality k such that the graph G − Vk is a tree but for any subset Vk−1 ⊂ V(G) of cardinality k − 1, the graph G − Vk−1 is not a tree. In this work, we find a sharp lower and some sharp upper bounds for this new sum‐connectivity index.
Cholecystokinin Expression in the Development of Myocardial Hypertrophy
Authors: Han Zhongshu , Bi Sheng , Xu Yongsheng , Dong Xiaoying , Mei Lixia , Lin Hailong , Li Xueqi
Published: August 2021

Background. Expression of cholecystokinin is found in myocardial tissues as a gastrointestinal hormone and may be involved in cardiovascular regulation. However, it is unclear whether there is an increase in cholecystokinin expression in myocardial hypertrophy progression induced by abdominal aortic constriction. The study is aimed at exploring the relationship between cholecystokinin expression and myocardial hypertrophy. Methods. We randomly divided the 70 Sprague-Dawley rats into two groups: the sham operation group and the abdominal aortic constriction group. The hearts of rats were measured by echocardiography, and myocardial tissues and blood were collected at 4 weeks, 8 weeks, and 12 weeks after surgery. Morphological changes were assessed by microscopy. The cholecystokinin expression was evaluated by immunochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Results. The relative protein levels of cholecystokinin were significantly increased in the abdominal aortic constriction groups compared with the corresponding sham operation groups at 8 weeks and 12 weeks. The cholecystokinin mRNA in the abdominal aortic constriction groups was significantly higher than the time-matched sham operation groups. Changes in the left ventricular wall thickness were positively correlated with the relative protein levels of cholecystokinin and the mRNA of cholecystokinin. Conclusions. The development of myocardial hypertrophy can affect the cholecystokinin expression of myocardial tissues.
Antioxidant Mechanisms of the Oligopeptides (FWKVV and FMPLH) from Muscle Hydrolysate of Miiuy Croaker against Oxidative Damage of HUVECs
Authors: Wang Yue-Zhen , Wang Yu-Mei , Pan Xin , Chi Chang-Feng , Wang Bin
Published: August 2021

In this work, the antioxidant mechanisms of bioactive oligopeptides (FWKVV and FMPLH) from protein hydrolysate of miiuy croaker muscle against H2O2‐damaged human umbilical vein endothelial cells (HUVECs) were researched systemically. The finding demonstrated that the HUVEC viability treated with ten antioxidant peptides (M1 to M10) at 100.0 μM for 24 h was not significantly affected compared with that of the normal group (P < 0.05). Furthermore, FWKVV and FMPLH at 100.0 μM could very significantly enhance the viabilities (75.89 ± 1.79% and 70.03 ± 4.37%) of oxidative‐damaged HUVECs by H2O2 compared with those of the model group (51.66 ± 2.48%) (P < 0.001). The results indicated that FWKVV and FMPLH played their protective functions through increasing the levels of antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) and decreasing the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) in oxidative‐damaged HUVECs in a dose‐dependent manner. In addition, the comet assay revealed that FWKVV and FMPLH could dose‐dependently protect deoxyribonucleic acid (DNA) from oxidative damage in the HUVEC model. These results suggested that antioxidant pentapeptides (FWKVV and FMPLH) could serve as potential antioxidant additives applied in the food products, pharmaceuticals, and health supplements.
Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: August 2021

Purpose:

There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor.

Experimental Design:

We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype.

Results:

Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the “granulocytic–myeloid-derived suppressor cell (G-MDSC) dominant” cluster, with high number of HLA-DR− CD14− myeloid cells; subtype II, the “immune exhausted” cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the “immune desert” cluster, with few immune cells. Immune cell–rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors.

Conclusions:

This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the “immune exhausted” subtype of patients with CHS.
A Longitudinal Cohort Study of Precocious Puberty and Autism Spectrum Disorder
Authors: Geier David A. , Geier Mark R.
Published: August 2021

Introduction: Autism spectrum disorder (ASD) is defined by persistent deficits in communication, socialization, and stereotypic behaviors. It was previously hypothesized that hormone dysfunction is a frequent occurrence among children diagnosed with an ASD. Objectives: A hypothesis-testing epidemiological study examined the relationship between precocious puberty (PP) (a known disorder of childhood sex hormone dysfunction) and ASD diagnoses. Methods: The Independent Healthcare Research Database is composed of de-identified linked eligibility and claims health-care records prospectively generated from the Florida Medicaid system. A cohort of 101,736 children eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth were examined using SAS and StatsDirect software. There were 1,593 children (15,738 person-years) in the ASD diagnosed cohort utilizing the Diagnostic and Statistical Manual of Mental Disorders, 4th revision criteria (the International Code for Disease, 9th revision [ICD-9] codes: 299.00 or 299.80) and 100,143 children (996,835 person-years) in the undiagnosed cohort. Results: The incidence rate of PP (ICD-9 code: 259.1) was examined using Cox proportional hazards ratio (HR) and frequency models. PP per 10,000 person-years in the ASD cohort (43.2) relative to the undiagnosed cohort (13.7) was significantly increased in frequency modeling (risk ratio = 3.15, p < 0.0001) and Cox proportional HR modeling (adjusted HR = 4.64, p < 0.0001). Further analyses revealed the incidence rate of PP diagnosed after 3 years of age was significantly increased (adjusted HR = 5.16, p < 0.0001) in the ASD cohort relative to the undiagnosed cohort but not for the incidence rate of PP diagnosed before 3 years (adjusted HR = 1.57, p = 0.44). Conclusion: This hypothesis-testing study provides strong evidence of an increased incidence rate of PP among children diagnosed with an ASD.
Apresentação V10 N01
Authors: Vicente Eduardo
Published: August 2021

Apresentação da edição
A review of the black species of Cyclocephala Dejean (Coleoptera: Scarabaeidae: Dynastinae) from Colombia
Authors: NEITA-MORENO JHON C.
Published: August 2021

The black species of the genus Cyclocephala Dejean (Coleoptera: Scarabaeidae: Dynastinae: Cyclocephalini) from Colombia are reviewed. I define species groups based on the morphology of adults, re-describe those species occurring in Colombia, describe two new species (Cyclocephala santandereana new species and Cyclocephala arhuacana new species), list the species reported for Colombia, provide a key to identify groups and the species within each group, and present species distribution and life history data. This review includes the Cyclocephala cribrata species group previously defined with C. boucheri Dechambre, C. carbonaria Arrow, C. cribrata Burmeister, C. dechambrei Dupuis, C. boliviana Dechambre, C. dilatata (Prell), C. ergastuli Dechambre, C. latipennis Arrow, C. marqueti Dechambre, C. proxima Dechambre, C. rogerpauli Moore, Branham, & Cave, and C. variolosa Burmeister. The Cyclocephala fasciolata species group contains C. abrelata Ratcliffe & Cave, C. brevipennis Endrödi, C. fasciolata Bates, C. melane Bates, and Cyclocephala santandereana new species. The Cyclocephala ligyrina species group has C. arhuacana new species, C. dalensi Ponchel, C. dyscinetoides Dechambre, C. endroedyyoungai Endrödi, C. kaszabi Endrödi, C. ligyrina Bates, Cyclocephala nigerrima Bates, C. rufa Endrödi, and C. scarabaeina (Gyllenhal). Cyclocephala carinatipennis Martínez & Morón is proposed as a new junior synonym of C. rufa Endrödi. A larva of the Cyclocephala cribrata species group is described for the first time. An analysis of the characters of the adults and the described larva of the species group is performed to imply phylogenetic implications. New country records of C. dalensi and C. marqueti are recorded for Colombia.
Molecular phylogeny of pimoid spiders and the limits of Linyphiidae, with a reassessment of male palpal homologies (Araneae, Pimoidae)
Authors: HORMIGA GUSTAVO , KULKARNI SIDDHARTH , DA SILVA MOREIRA THIAGO , DIMITROV DIMITAR
Published: August 2021

We address the phylogenetic relationships of pimoid spiders (Pimoidae) using a standard target-gene approach with an extensive taxonomic sample, which includes representatives of the four currently recognized pimoid genera, 26 linyphiid genera, a sample of Physoglenidae, Cyatholipidae and one Tetragnathidae species. We test the monophyly of Pimoidae and Linyphiidae and explore the biogeographic history of the group. Nanoa Hormiga, Buckle and Scharff, 2005 and Pimoa Chamberlin & Ivie, 1943 form a clade which is the sister group of a lineage that includes all Linyphiidae, Weintrauboa Hormiga, 2003 and Putaoa Hormiga and Tu, 2008. Weintrauboa, Putaoa, Pecado and Stemonyphantes form a clade (Stemonyphantinae) sister to all remaining linyphiids. We use the resulting optimal molecular phylogenetic tree to assess hypotheses on the male palp sclerite homologies of pimoids and linyphiids. Pimoidae is redelimited to only include Pimoa and Nanoa. We formalize the transfer from Pimoidae of the genera Weintrauboa and Putaoa to Linyphiidae, re-circumscribe the linyphiid subfamily Stemonyphantinae, and offer revised morphological diagnoses for Pimoidae and Linyphiidae.
Contribution to the knowledge of Chinese Phasmatodea X: Eight new species of Cnipsomorpha from China (Phasmatidae: Clitumninae: Medaurini)
Authors: HO GEORGE WAI-CHUN
Published: August 2021

Eight new species of Cnipsomorpha Hennemann, Conle, Zhang & Liu, 2008 are described from China. They are namely, Cnipsomorpha inflexa sp. nov., Cnipsomorpha jinpingensis sp. nov., Cnipsomorpha nigromaculata sp. nov., Cnipsomorpha nigrospina sp. nov., Cnipsomorpha polyspina sp. nov., Cnipsomorpha serratitibia sp. nov., Cnipsomorpha trituberculata sp. nov. and Cnipsomorpha viridis sp. nov. A key to the species and list of the species of Cnipsomorpha are provided.
Two new species of Onciderini Thomson, 1860 (Cerambycidae: Lamiinae) from Mexico and Honduras
Authors: PÉREZ-FLORES OSCAR , NEARNS EUGENIO H.
Published: August 2021

Hesychotypa albofasciata sp. nov. from Mexico (Veracruz) and Honduras, and Tulcus santossilvai sp. nov. from Mexico (Oaxaca) are described and illustrated. Distinguishing characters from closely related species are provided and discussed.
Trends and Variability of North American Cool-Season Extratropical Cyclones: 1979–2019
Authors: Fritzen Robert , Lang Victoria , Gensini Vittorio A.
Published: August 2021

Extratropical cyclones are the primary driver of sensible weather conditions across the mid-latitudes of North America, often generating various types of precipitation, gusty non-convective winds, and severe convective storms throughout portions of the annual cycle. Given ongoing modifications of the zonal atmospheric thermal gradient due to anthropogenic forcing, analyzing the historical characteristics of these systems presents an important research question. Using the North American Regional Reanalysis, boreal cool-season (October–April) extratropical cyclones for the period 1979–2019 were identified, tracked, and classified based on their genesis location. Additionally, bomb cyclones—extratropical cyclones that recorded a latitude normalized pressure fall of 24 hPa in 24-hr—were identified and stratified for additional analysis. Cyclone lifespan across the domain exhibits a log-linear relationship, with 99% of all cyclones tracked lasting less than 8 days. On average, ≈ 270 cyclones were tracked across the analysis domain per year, with an average of ≈ 18 year−1 being classified as bomb cyclones. The average number of cyclones in the analysis domain has decreased in the last 20 years from 290 year−1 during the period 1979–1999 to 250 year−1 during the period 2000–2019. Spatially, decreasing trends in the frequency of cyclone track counts were noted across a majority of the analysis domain, with the most significant decreases found in Canada’s Northwest Territories, Colorado, and east of the Graah mountain range. No significant interannual or spatial trends were noted with bomb cyclone frequency.
Patient, parent and educator perspectives on paediatric concussion
Authors: Grool Anne M , DeMatteo Carol , Reed Nick , Newhook Dennis , Zemek Roger
Published: August 2021

Background

Past research on paediatric concussion awareness, management, impact and outcome priorities has focused on health care professionals and sports organizations, yet little is known about patient, parent and educator perspectives.

Methods

To address this knowledge gap, we conducted a qualitative descriptive study using semi-structured interviews with three participant groups: patient-participants including children with acute or chronic concussion; parent-participants including caregivers of children at risk for or with history of concussion; and educator-participants including teachers and athletic coaches from three Ontario secondary schools. We designed our interview guide to elicit participants’ perspectives across four domains: concussion awareness, concussion experience, support and resources, and outcome priorities. We analyzed our resultant data using a qualitative content analysis approach.

Results

Nine paediatric patient-participants, 17 parent-participants, and 14 educator-participants completed the study. Participants described concussion as a serious health concern and attributed greater concussion awareness to increased media attention and concussion protocol implementation within schools/sports. While most educator-participants regarded concussion protocols positively, some feared student manipulation. Parent- and educator-participants desired consistent information and resources from reliable sources. The impact of concussion ranged from a few days to prolonged absences (from school, sports, and socializing) and necessitated accommodations in both academic and sport settings. Short-term problems (e.g., decreased peer-contact) primarily troubled patient-participants, whereas long-term problems (e.g., impaired academics, psychological stress) concerned parent and educator groups.

Conclusion

Patients, parents and educators worry about the consequences of paediatric concussion. Initial concussion recovery in youth should focus on a timely return to academics and on minimizing social isolation by ensuring peer-contact during recovery.
Insertion of atypical glycans into the tumor antigen-binding site identifies DLBCLs with distinct origin and behavior
Authors: Chiodin Giorgia , Allen Joel D. , Bryant Dean J. , Rock Philip , Martino Enrica A. , Valle-Argos Beatriz , Duriez Patrick J. , Watanabe Yasunori , Henderson Isla , Blachly James S. , McCann Katy J. , Strefford Jonathan C. , Packham Graham , Geijtenbeek Teunis B. H. , Figdor Carl G. , Wright George W. , Staudt Louis M. , Burack Richard , Bowden Thomas A. , Crispin Max , Stevenson Freda K. , Forconi Francesco
Published: August 2021

Glycosylation of the surface immunoglobulin (Ig) variable region is a remarkable follicular lymphoma–associated feature rarely seen in normal B cells. Here, we define a subset of diffuse large B-cell lymphomas (DLBCLs) that acquire N-glycosylation sites selectively in the Ig complementarity-determining regions (CDRs) of the antigen-binding sites. Mass spectrometry and X-ray crystallography demonstrate how the inserted glycans are stalled at oligomannose-type structures because they are buried in the CDR loops. Acquisition of sites occurs in ∼50% of germinal-center B-cell–like DLBCL (GCB-DLBCL), mainly of the genetic EZB subtype, irrespective of IGHV-D-J use. This markedly contrasts with the activated B-cell–like DLBCL Ig, which rarely has sites in the CDR and does not seem to acquire oligomannose-type structures. Acquisition of CDR-located acceptor sites associates with mutations of epigenetic regulators and BCL2 translocations, indicating an origin shared with follicular lymphoma. Within the EZB subtype, these sites are associated with more rapid disease progression and with significant gene set enrichment of the B-cell receptor, PI3K/AKT/MTORC1 pathway, glucose metabolism, and MYC signaling pathways, particularly in the fraction devoid of MYC translocations. The oligomannose-type glycans on the lymphoma cells interact with the candidate lectin dendritic cell–specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN), mediating low-level signals, and lectin-expressing cells form clusters with lymphoma cells. Both clustering and signaling are inhibited by antibodies specifically targeting the DC-SIGN carbohydrate recognition domain. Oligomannosylation of the tumor Ig is a posttranslational modification that readily identifies a distinct GCB-DLBCL category with more aggressive clinical behavior, and it could be a potential precise therapeutic target via antibody-mediated inhibition of the tumor Ig interaction with DC-SIGN–expressing M2-polarized macrophages.
T-follicular helper cell expansion and chronic T-cell activation are characteristic immune anomalies in Evans syndrome
Authors: Kumar Deepak , Prince Chengyu , Bennett Carolyn M. , Briones Michael , Lucas Laura , Russell Athena , Patel Kiran , Chonat Satheesh , Graciaa Sara , Edington Holly , White Michael H. , Kobrynski Lisa , Abdalgani Manar , Parikh Suhag , Chandra Sharat , Bleesing Jack , Marsh Rebecca , Park Sunita , Waller Edmund K. , Prahalad Sampath , Chandrakasan Shanmuganathan
Published: August 2021

Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity. Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HCs). Compared with patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T-cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high immunoglobulin G (IgG) in most pES at presentation, class-switched memory B cells were decreased. Within the cTfh subset, we noted features of postactivation exhaustion with upregulation of several canonical checkpoint inhibitors. T-cell receptor β chain (TCR-β) repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HCs. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T-cell abnormalities as patients with low IgG. Because genetic defects have been identified in less than half of patients with pES, our findings of similar immune abnormalities across all patients with pES help establish a common characteristic immunopathology in pES, irrespective of the underlying genetic etiology.
A young woman presented with massive pulmonary embolism with inferior vena cava thrombus as a complication of nephrotic syndrome: a case report
Authors: Jeele Mohamed Osman Omar , Addow Rukia Omar Barei , Mohamud Mohamed Farah Yusuf
Published: August 2021

Nephrotic syndrome (NS) was first described in 1827 as the presence of proteinuria of ≥ 3.5 g/24 h, hypoalbuminemia < 3.0 g/dl, peripheral edema, hyperlipidemia, lipiduria, and increased thrombotic risk. Nephrotic syndrome has an incidence of three cases per 100,000 each year in adults. Nephrotic syndrome also has serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. The pathophysiology of hypercoagulability in the nephrotic syndrome is due to an imbalance of prothrombotic and antithrombotic factors, as well as impaired thrombolytic activities.

Here, we will present a 19-year-old woman who presented to the emergency department complaining of chest pain and shortness of breath for 3 days. The patient was quickly diagnosed with pulmonary embolism and inferior vena cava thrombosis as a complication of nephrotic syndrome, allowing prompt initiation of anticoagulant therapy. After 2 weeks of admission, the patient’s condition resolved, her laboratory results returned to almost normal and the patient was discharged with oral prednisolone, coumadin, atorvastatin, and ramipril. We aim to determine which is the likely cause of pulmonary embolism in patients with nephrotic syndrome.
Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo
Authors: Grebinyk Anna , Prylutska Svitlana , Grebinyk Sergii , Evstigneev Maxim , Krysiuk Iryna , Skaterna Tetiana , Horak Iryna , Sun Yanfang , Drobot Liudmyla , Matyshevska Olga , Prylutskyy Yuriy , Ritter Uwe , Frohme Marcus
Published: August 2021

Background

Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC).

Methods

C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg).

Results

Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected.

Conclusions

This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma.

Graphical abstract
The effect of home visits as an additional recruitment step on the composition of the final sample: a cross-sectional analysis in two study centers of the German National Cohort (NAKO)
Authors: Krist Lilian , Bedir Ahmed , Fricke Julia , Kluttig Alexander , Mikolajczyk Rafael
Published: August 2021

Background

Participation in epidemiologic studies has been declining over the last decades. In addition to postal invitations and phone calls, home visits can be conducted to increase participation. The aim of this study was therefore to evaluate the effects of home visits in terms of response increase and composition of the additionally recruited and final sample.

Methods

In the framework of the German National Cohort (NAKO) recruitment process, two of 18 study centers, Halle (Saale) and Berlin-Center, performed home visits as additional recruitment step after postal invitation and reminders. Response increase was calculated and differences between participants recruited via home visits and standard recruitment were examined. Proportions are presented as percentages with 95%-confidence intervals.

Results

In the general population in Halle, 21.3-22.8% participated after postal invitation and two reminders in the five assessed recruitment waves. The increase of the overall response was 2.8 percentage points (95%confidence interval: 1.9-4.0) for home visits compared to 2.4 percentage points (95%CI: 1.7-3.3) for alternatively sent third postal reminder. Participants recruited via home visits had similar characteristics to those recruited via standard recruitment. Among persons of Turkish descent in Berlin-Center site of the NAKO, home visits conducted by native speakers increased the participation of women, persons living together with their partner, were born in Turkey, had lower German language skills, lower-income, lower education, were more often smokers and reported more often diabetes and depression to a degree which changed overall estimates for this subsample.

Conclusions

As an additional recruitment measure in the general population, home visits increased response only marginally, and the through home visits recruited participants did not differ from those already recruited. Among persons with migration background, home visits by a native speaker increased participation of persons not reached by the standard recruitment, but the effects of using a native speaker approach could not be separated from the effect of home visits.
Long-term prognosis after endoscopic submucosal dissection for colorectal tumors in patients aged over 80 years
Authors: Nishimura Tomoyuki , Oka Shiro , Tanaka Shinji , Kamigaichi Yuki , Tamari Hirosato , Shimohara Yasutsugu , Okamoto Yuki , Inagaki Katsuaki , Matsumoto Kenta , Tanaka Hidenori , Yamashita Ken , Ninomiya Yuki , Kitadai Yasuhiko , Arihiro Koji , Chayama Kazuaki
Published: August 2021

Background

In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years.

Methods

ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months.

Results

The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients.

Conclusions

ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.
Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model
Authors: Kajiwara Koichiro , Sawa Yoshihiko
Published: August 2021

Background

The overexpression of sodium-glucose cotransporter 2 (SGLT2) in diabetic kidneys has been reported. It has also been established that the diabetic glomerular endothelium expresses the toll-like receptors TLR2 and TLR4. The present study aims to examine the renal SGLT2 induction by the TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharide (Pg-LPS) in mouse diabetic nephropathy.

Methods

Immunohistochemical study and tissue RT-PCR analyses were performed on mouse kidneys in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), in healthy ICR mice administered Pg-LPS (LPS-ICR), and in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ).

Results

In the quantitative analysis of blood sugar levels, the mean time to reach 600 mg/dl was shorter in the LPS-STZ than in the STZ-ICR kidneys. The rise in blood glucose levels was significantly steeper in the LPS-STZ than in the STZ-ICR kidneys. According to these data the LPS-STZ model suggests a marked glucose intolerance. The expression of SGLT2 was significantly stronger in the whole of the renal parenchyma of the LPS-STZ than in the LPS-ICR or in the STZ-ICR. The expression of SGLT2 was observed both in the renal tubules and around the renal tubules, and in the glomeruli of the LPS-STZ kidneys. In the analysis by tissue real-time PCR and cell ELISA, the expression of the SGLT2 gene and protein was significantly stronger in the LPS-STZ than in the LPS-ICR or in the STZ-ICR. There were no differences in the renal SGLT2 production in the LPS-ICR and the STZ-ICR kidneys.

Conclusions

Abnormally high renal expression of SGLT2 occurs in diabetic kidneys with P. gingivalis LPS. Periodontitis may be an exacerbating factor in diabetic nephropathy as well as in diabetes.
Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b: post-hoc analysis of a 2-year, prospective, international, observational study
Authors: Patti Francesco , Penaherrera Javier Nicolas , Zieger Lorissa , Wicklein Eva-Maria
Published: August 2021

Background

Despite trends towards the increased age of patients living with multiple sclerosis (MS), little is known about the response of older adults with MS to disease-modifying therapies (DMTs). Thus, a post-hoc analysis was undertaken using data from a 2-year, international, non-interventional, prospective cohort study (NCT00787657; BEACON: BEtaferon prospective study on Adherence, COping and Nurse support) of patients above the age of 40 years with MS and starting interferon beta-1b (IFNB-1b) treatment within 6 months before study entry.

Methods

Middle-aged and older patients with MS were divided into two sub-groups: 41–50 years and > 50 years. Treatment with IFNB-1b started within 6 months before study entry. Patients were followed-up for a 2-year observation period. Assessments included disease history and course, annualised relapse rate (ARR), Expanded Disability Scale Score (EDSS), treatment adherence, Hospital Anxiety and Depression Scale (HADS), and adverse events (AE).

Results

At baseline, the intention-to-treat (ITT) population (n = 481) aged 41–50 years (n = 327) and > 50 years (n = 154), had mean (standard deviation [SD]) ages of 45.1 (2.8) and 56.2 (4.2) years, maximum age of 72 years, and duration of MS since onset of symptoms of 3.9 (5.2) and 5.9 (7.1) years, respectively. At baseline, the proportion of patients with relapsing–remitting MS (RRMS) was 96.3 and 94.9 %, and secondary progressive MS (SPMS) was 3.7 and 5.1 %, in the 41–50 and > 50 years sub-groups, respectively. The ARR in the 2 years before study start was 0.93 (0.48) and 0.86 (0.54) for the 41–50 and > 50 years groups, respectively, and decreased since study start to 0.20 (1.09) and 0.07 (0.37), respectively. The percentage of patients with anxiety and depression, as measured by HADS, were stable over the study period. Polypharmacy (five or more medications) was seen in 32.3 and 41.2 % of patients aged 41–50 and > 50 years. No unexpected AEs were reported.

Conclusions

This study provides observational data on patients between 40 and 72 years of age, suggesting that IFNB-1b can be an effective and well-tolerated treatment option in MS patients of advanced age.

Trial registration

ClinicalTrials.gov, NCT00787657.
Randomized phase II study of SOX+B-mab versus SOX+C-mab in patients with previously untreated recurrent advanced colorectal cancer with wild-type KRAS (MCSGO-1107 study)
Authors: Nishizawa Yujiro , Haraguchi Naotsugu , Kim Hirotoshi , Ide Yoshihito , Nakata Ken , Okamura Shu , Kudo Toshihiro , Satoh Taroh , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Murata Kohei , Doki Yuichiro , Eguchi Hidetoshi
Published: August 2021

Background

Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS.

Methods

This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled.

Results

Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively).

Conclusions

The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen.

Trial registration

UMIN Clinical Trials Registry (UMIN000006706).

Date of registration: NOV/11/2011.

URL of trial registry record:

https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920
Gliotic opaque posterior hyaloid membrane separation: report of two cases
Authors: Hosaka Fumio , Saito Wataru , Kase Satoru , Ishida Susumu
Published: August 2021

Background

To report two cases with idiopathic unilateral diffuse opacification of the posterior hyaloid membrane (PHM) completely separated from the retina, the mechanism of which is possibly due to glial cell proliferation and migration.

Case presentation

Two Japanese women at age 75 and 84 with no systemic or ocular history developed diffuse opacification in one eye resembling a ground glass sheet almost all over the surface of the PHM, but not within the vitreous gel or fluid. The retinas were funduscopically normal; however, optical coherence tomography demonstrated hyperreflective icicle-like anterior protrusions from the surface of the fovea. The patients received pars plana vitrectomy, resulting in visual improvement. Cell block preparations of the vitreous in one case revealed a cluster of cells immunoreactive for glial fibrillary acidic protein in consistence with gliosis, while denying vitreoretinal lymphoma from lack of atypical cells and vitreous amyloidosis due to no staining for Congo red or direct fast scarlet. The lesions did not recur during follow-up with no new funduscopic abnormalities.

Conclusions

To our knowledge, this is the first to demonstrate such peculiar cases of vitreous opacity with idiopathic and unilateral onset. Histological assessments revealed the possible pathogenesis of gliotic opaque PHM separation to cause its ground-glass-sheet appearance.
Trajectories of loneliness and objective social isolation and associations between persistent loneliness and self-reported personal recovery in a cohort of secondary mental health service users in the UK
Authors: Ma Ruimin , Wang Jingyi , Lloyd-Evans Brynmor , Marston Louise , Johnson Sonia
Published: August 2021

Background

Loneliness is a frequent and distressing experience among people with mental health problems. However, few longitudinal studies have so far investigated the trajectories of loneliness and objective social isolation, and the extent to which both issues may impact mental health outcomes among mental health service users. Therefore, this study aims to describe the trajectories of loneliness and objective social isolation and their associations with self-rated personal recovery among people leaving crisis resolution teams (CRTs).

Methods

A total of 224 participants receiving care from CRTs (recruited for a large multi-site randomised controlled trial) were included in this longitudinal cohort study. They completed the eight-item University of California at Los Angeles Loneliness Scale (ULS-8), Lubben-Social Network Scale (LNSN-6), and the Questionnaire about the Process of Recovery (QPR) (primary outcome) at baseline, 4- and 18-month follow-up, as well as baseline sociodemographic and clinical variables.

Results

We compared groups who were persistently lonely (at all time points), intermittently lonely (at one or two time points) and never lonely. After adjusting for all potential confounders and baseline predictive variables, persistent severe loneliness was associated with worse personal recovery at 18-month follow-up compared with the never lonely (reference group) (coef. = − 12.8, 95% CI -11.8, − 3.8,p < .001), as was being intermittently lonely (coef. = − 7.8, 95% CI -18.8, − 6.8, p < .001). The persistently objectively social isolated group (coef. = − 9.8, 95% CI -15.7, − 3.8,p = .001) also had poorer self-rated recovery at 18-month follow-up than those who were not socially isolated at any timepoint (i.e., reference category).

Conclusion

Results suggest that both persistent loneliness and objective social isolation are associated with poorer self-rated recovery following a crisis, compatible with a causal relationship. These findings suggest a potential role for interventions aimed at alleviating loneliness and objective social isolation in improving recovery outcomes for people with mental health symptoms. Increased awareness of both issues among health practitioners is also warranted.