bluuebunny/crossref_metadata_2025 huggingface dataset:
A modified version of the mental health literacy scale (MHLS) in Iranian people
Authors: Nejatian Mahbobeh , Tehrani Hadi , Momeniyan Vahideh , Jafari Alireza
Published: January 2021

Background

The risk rate for the lifetime prevalence of any mental disorder is calculated as 50%, and the prevalence of mental disorders has an increasing trend. So, this study aimed to evaluate the Mental Health Literacy Scale (MHLS) among Iranian people.

Methods

This cross-sectional study was conducted with a multi-stage sampling method with 1273 people in the general population. After searching and reviewing various sources, the research team decided to use the questionnaire of MHLS with 35 items and six attributes that were measured and developed by O’Connor et al. The face, content, and construct validity (Confirmatory factor analysis) were used for validation of MHLS. McDonald’s omega coefficient and Cronbach’s alpha coefficient were used to calculate the reliability of MHLS. Confirmatory factor analysis was performed using AMOS software Version 24.

Results

In the CFA test, the six items were deleted. The final modified version of the MHLS included a total of 29 items with six attributes consisted of (a) knowledge of where to seek information (4 items), (b) ability to recognize disorders (8 items), (c) knowledge of self-treatment (2 items), (d) knowledge of risk factors and causes (2 items), (e) attitudes that promote recognition or appropriate help-seeking behavior (10 items), and (f) knowledge of professional help available (3 items). Based on the results of reliability, McDonald’s omega coefficient and Cronbach’s alpha coefficient for all attributes of MHLS were 0.797 and 0.789, respectively.

Conclusion

Due to the lack of appropriate instruments for measuring mental health literacy in the Iranian population, the modified version of MHLS with 29 items and six attributes can be considered as a valid and reliable instrument for this purpose.
Polytobacco use among a nationally-representative sample of black high school students
Authors: Gilreath Tamika D. , Dangerfield Derek T. , Montiel Ishino Francisco A. , Hill Ashley V. , Johnson Renee M.
Published: January 2021

Background

Studies of the patterns of polytobacco use have increased. However, understanding the patterns of using multiple tobacco products among Black adolescents is minimal. This study identified the patterns of polytobacco use among U.S. Black adolescents.

Methods

Latent class analysis (LCA) was used to identify patterns of adolescent polytobacco use among a representative sample of Black youth from the 2017 Youth Risk Behavior Survey (n = 2782). Ever and recent (past 30 day) use of cigarettes, electronic cigarettes, cigars, and dip or chewing tobacco were used as latent class indicators. Multinomial regression was conducted to identify the association if smoking adjusting for sex, age, grade, and marijuana use.

Results

Most students were in the 9th grade (29%), e-cigarette users (21%) and were current marijuana users (25%). Three profiles of tobacco use were identified: Class 1: Non-smokers (81%), Class 2: E-cigarette Users (14%), and Class 3: Polytobacco Users (5%). Black adolescent Polytobacco users were the smallest class, but had the highest conditional probabilities of recent cigarette use, e-cigarette use, ever smoking cigars or chewing tobacco. Ever and current use of marijuana were associated with increased odds of being in the e-cigarette user versus non-smoker group, and current marijuana use was associated with increased odds of polytobacco use (aOR = 24.61, CI = 6.95–87.11).

Conclusions

Findings suggests the need for targeted interventions for reducing tobacco use and examining the unique effects of polytobacco use on Black adolescents. Findings confirm a significant association of marijuana use with tobacco use.
A comparison of glycemic parameters and their relationship with C-peptide and Proinsulin levels during partial remission and non-remission periods in children with type 1 diabetes mellitus - a cross-sectional study
Authors: Yeşiltepe-Mutlu Gül , Çapacı Merve , Can Ecem , Gökçe Tuğba , Bayrakçı Gizem , Muradoğlu Serra , İncir Said , Çakır Esra Papatya , Hatun Şükrü
Published: January 2021

Background

Currently, there is a lack of data relating to glycemic parameters and their relationship with C-peptide (CP) and proinsulin (PI) during the partial remission period (PRP) in type 1 diabetes mellitus (T1D). The aim of this study was to evaluate glycemic parameters in children with T1D who are in the PRP using intermittently scanned continuous glucose monitoring systems (isCGMS) and to investigate any relationships between CP and PI levels.

Methods

The study included 21 children who were in the PRP and 31 children who were not. A cross-sectional, non-randomized study was performed. Demographic, clinical data were collected and 2 week- isCGMS data were retrieved.

Results

The Serum CP showed a positive correlation with time-in-range in the PRP (p:0.03), however PI showed no correlations with glycemic parameters in both periods. The Serum CP and PI levels and the PI:CP ratio were significantly higher in the PRP group than in the non-PRP group. In the non-PRP group, the PI level was below 0.1 pmol/L (which is the detectable limit) in only 2 of the 17 cases as compared with none in the PRP group. Similarly, only 2 of the 17 children in the non-PRP group had CP levels of less than 0.2 nmol / L, although both had detectable PI levels. Overall time-in-range (3. 9-1.0 mmol/L) was significantly high in the PRP group. In contrast, the mean sensor glucose levels, time spent in hyperglycemia, and coefficient of variation levels (32.2vs 40.5%) were significantly lower in the PRP group.

Conclusions

Although the mean glucose and time in range during the PRP was better than that in the non-PRP group, the glycemic variability during this period was not as low as expected. While the CP levels showed an association with TIR during the PRP, there was no correlation between PI levels and glycemic parameters. Further studies are needed to determine if PI might prove to be a useful parameter in clinical follow-up.
Health care needs of elderly patients with lung, liver, or colon cancer in Taiwan
Authors: Lee Tzu-Yin , Susanti Henny Dwi , Hung Kuo-Chen , Yang Su-Yueh , Fang Hui-Fen , Tsai Jia-Ruey , Chiou Jeng-Fong , Chung Min-Huey
Published: January 2021

Background

Globally, different age groups in the elderly population have experienced major shifts over time. Human life expectancy doubled from the 19th to the twentieth century and has increased to 80 years in the twenty-first century. These conditions imply economic challenges and the increasing prevalence of certain health conditions. Old age is associated with increased care needs in various aspects of daily life. This study assessed the health care needs of elderly patients with lung, liver, and colorectal cancer in Taiwan and analyzed the factors underlying their needs.

Methods

This cross-sectional descriptive survey assessed 234 elderly patients with diagnosis of lung, liver, and colorectal cancer in Taiwan. We investigated their health care needs and daily living functions by using the Supportive Care Needs Survey and Karnofsky Performance Status, respectively.

Results

Patients required the most assistance in physical functioning and daily living. Patients aged ≥85 years required more care than those aged 65–74 years in terms of information access and sexuality needs. Patients with poor functional status required more care than those capable of undertaking normal activities. Patients diagnosed as having liver cancer required more care than those with lung or colorectal cancer. Patients with advanced cancer required more physical and daily care than those with early-stage cancer.

Conclusions

Patients’ health care needs differed with age, primary cancer site, and functional status. Patients aged ≥85 years and those with poor function, primary liver cancer, and advanced cancer had higher care needs.
Cranial morphology of captive mammals: a meta-analysis
Authors: Siciliano-Martina Leila , Light Jessica E. , Lawing A. Michelle
Published: January 2021

Background

Captive facilities such as zoos are uniquely instrumental in conservation efforts. To fulfill their potential as bastions for conservation, zoos must preserve captive populations as appropriate proxies for their wild conspecifics; doing so will help to promote successful reintroduction efforts. Morphological changes within captive populations may be detrimental to the fitness of individual animals because these changes can influence functionality; thus, it is imperative to understand the breadth and depth of morphological changes occurring in captive populations. Here, we conduct a meta-analysis of scientific literature reporting comparisons of cranial measures between captive and wild populations of mammals. We investigate the pervasiveness of cranial differences and whether cranial morphological changes are associated with ecological covariates specific to individual species, such as trophic level, dietary breadth, and home range size.

Results

Cranial measures of skull length, skull width, and the ratio of skull length-to-width differed significantly between many captive and wild populations of mammals reported in the literature. Roughly half of captive populations differed from wild populations in at least one cranial measure, although the degree of changes varied. Carnivorous species with a limited dietary breadth displayed the most consistent changes associated with skull widening. Species with a more generalized diet displayed less morphological changes in captivity.

Conclusions

Wild and captive populations of mammals differed in cranial morphology, but the nature and magnitude of their cranial differences varied considerably across taxa. Although changes in cranial morphology occur in captivity, specific changes cannot be generalized for all captive mammal populations. The nature of cranial changes in captivity may be specific to particular taxonomic groups; thus, it may be possible to establish expectations across smaller taxonomic units, or even disparate groups that utilize their cranial morphology in a similar way. Given that morphological changes occurring in captive environments like zoos have the potential to limit reintroduction success, our results call for a critical evaluation of current captive husbandry practices to prevent unnecessary morphological changes.
Ethnobotanical characterization of medicinal plants used in Kisantu and Mbanza-Ngungu territories, Kongo-Central Province in DR Congo
Authors: Pathy Kibungu Kembelo , Flavien Nzuki Bakwaye , Honoré Belesi Katula , Vanhove Wouter , Van Damme Patrick
Published: January 2021

Background

The phytotherapeutic knowledge of the Kongo people in the territories of Kisantu and Mbanza-Ngungu in Kongo-Central Province (DR Congo) is rapidly eroding. To document the remaining knowledge, we conducted an ethnobotanical survey on the most important medicinal plant species and diseases treated with them, as well as plants with therapeutic potential. We also checked for the cultural similarity in medicinal plant knowledge between the two territories and how knowledge about Kongo medicinal plants differs between different social groups.

Methods

From June 2017 until February 2018 and from February 2019 until April 2019, we conducted a survey with 188 phytotherapists, selected using the snowball method and surveyed using semi-structured interviews. Voucher specimens were taken for identification. Ethnobotanical data were analyzed using medicinal use value (UVs), informant agreement ratio (IARs), informant consensus factor (ICF), and species therapeutic potential (STP). Rahman’s similarity index was used for ethno-cultural comparison of medicinal plant knowledge between the two communities. Medicinal knowledge between different social groups was analyzed using non-parametric tests and Poisson regression.

Results

A total of 231 plants (i.e., 227 botanical species, representing 192 genera and 79 families) were reportedly used to treat 103 diseases. Most abundant taxa were reported for the Fabaceae family (including 11.9% of species and 10.9% of genera). Most reported species (45.0%) were from anthropized areas. Leaves (39.4%), herbs (37.1%), decoction (41.7%), and oral ingestion (72%) were the most frequently cited plant part, botanical form, preparation, and administration method, respectively. Four of all inventoried species showed high UVS (> 0.05), whereas eight had an IAR of one. According to ICF, 31 diseases were mentioned. Highest ICF (≥ 0.4) was observed for hemorrhoids (0.44), amoebiasis (0.43), and itchy rash (0.42). Fifty-four plant species were identified as likely possessing an interesting therapeutic potential. Low ethno-cultural similarity in medicinal knowledge (RSI = 16.6%) was found between the two territories. Analysis of the Kongo medicinal plant knowledge showed that the mean number of reported species and diseases vary considerably depending on gender, type, and residence of therapists (P < 0.05).

Conclusion

Results prove that the Kongo phytopharmacopeia makes use of interesting medicinal plant species that could be further studied for conservation and pharmacological applications.
What interferes with conducting free lists? A comparative ethnobotanical experiment
Authors: Meireles Melise Pessôa Araujo , de Albuquerque Ulysses Paulino , de Medeiros Patrícia Muniz
Published: January 2021

Background

The free list, also written “freelist”, or “free recall”, is an ethnographic method that characterizes the local knowledge of a population about a given cultural domain. However, there is still much to elucidate about the variables that can influence the number of items that participants cite using this technique. This study applied a casual-comparative experimental design to analyze whether 3 months’ time, age, and external stimuli influence the similarity of plant free lists applied at different times.

Methods

Data was collected from 103 farmers from the rural community Alto dos Canutos, in the municipality of Picos, Piauí state, Brazil. Two free lists were conducted at two different times, with an interval of three months between them. Subsequently, the similarity between the first and second free lists of each participant was calculated using the Jaccard Similarity Index. The generalized linear model (GLM) with binomial errors and stepwise approach was used to analyze the effects of age and external stimuli on information collection when comparing free lists applied at different times.

Results

Participants’ age influenced the information that the free lists collected, demonstrating that the older the participants, the lower the similarity among the free lists. Among the external stimuli analyzed, only the presence of third parties influenced the content of the free lists at the time of the interview. However, contrary to expectations, third-party presence positively influenced the similarity of the lists.

Conclusion

The results show that the studied variables age and third-party presence can influence the capture of knowledge. These findings warrant future research into the influences’ causes and their potential mitigation, e.g., by isolation or by breaking the medicinal plant domain into focused sub-domains and conducting simpler, successive free-lists, which can mitigate memory issues.
Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10
Authors: Chen Fangyu , Xu Bing , Li Jie , Yang Xi , Gu Junjie , Yao Xijuan , Sun Xinchen
Published: January 2021

Background

Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear.

Methods

Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter.

Results

Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis.

Conclusions

Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.
A validity study of the rapid emergency Triage and treatment system for children
Authors: Ødegård Siv Steinsmo , Tran Thuy , Næss-Pleym Lars E. , Risnes Kari , Døllner Henrik
Published: January 2021

Background

The Scandinavian Rapid Emergency Triage and Treatment System-pediatric (RETTS-p) is a reliable triage system that includes both assessment of vital parameters and a systematic approach to history and symptoms. In Scandinavia, the system is used in most pediatric emergency departments (PED). We aimed to study the validity of RETTS-p.

Methods

We conducted a study based on triage priority ratings from all children assessed in 2013 and 2014 to the PED at St. Olavs University Hospital Trondheim, Norway. Patients were assigned one of four priority ratings, based on the RETTS-p systematic evaluation of individual disease manifestations and vital parameter measurements. In the absence of a gold-standard for true disease severity, we assessed whether priority ratings were associated with 3 proxy variables: 1) hospitalization to the wards (yes vs. no), 2) length of hospital stay (≤ mean vs. > mean, and 3) referral to pediatric intensive care (yes vs. no). We further compared priority ratings with selected diagnoses and procedure codes at discharge.

Results

Six thousand three hundred sixty-eight children were included in the study. All analyses were performed in the entire population and separately in pediatric sub-disciplines, medicine (n = 4741) and surgery (general and neurosurgery) (n = 1306). In the entire population and the sub-disciplines, a high priority rate was significantly associated with hospitalization to wards, a longer hospital stay and referral to the pediatric intensive care unit compared to patients with low priority. We observed a dose-response relationship between increased triage code level and indicators of more severe disease (p-trend < 0.001). For the same three proxy variables, the sensitivity was 54, 61 and 83%, respectively, and the specificity 66, 62 and 57%, respectively. Subgroup analyzes within the most common complaints, demonstrated that more severe conditions were higher prioritized than less severe conditions for both medical and surgical patients. Overall, children with surgical diagnoses attained lower priority ratings than children with medical diagnoses.

Conclusions

RETTS-p priority ratings varies among a broad spectrum of pediatric conditions and mirror medical urgency in both medical and surgical disciplines. RETTS-p is a valid triage system for children as used in a university hospital setting.
Transposable element subfamily annotation has a reproducibility problem
Authors: Carey Kaitlin M. , Patterson Gilia , Wheeler Travis J.
Published: January 2021

Background

Transposable element (TE) sequences are classified into families based on the reconstructed history of replication, and into subfamilies based on more fine-grained features that are often intended to capture family history. We evaluate the reliability of annotation with common subfamilies by assessing the extent to which subfamily annotation is reproducible in replicate copies created by segmental duplications in the human genome, and in homologous copies shared by human and chimpanzee.

Results

We find that standard methods annotate over 10% of replicates as belonging to different subfamilies, despite the fact that they are expected to be annotated as belonging to the same subfamily. Point mutations and homologous recombination appear to be responsible for some of this discordant annotation (particularly in the young Alu family), but are unlikely to fully explain the annotation unreliability.

Conclusions

The surprisingly high level of disagreement in subfamily annotation of homologous sequences highlights a need for further research into definition of TE subfamilies, methods for representing subfamily annotation confidence of TE instances, and approaches to better utilizing such nuanced annotation data in downstream analysis.
Retroactive interference model of forgetting
Authors: Georgiou Antonios , Katkov Mikhail , Tsodyks Misha
Published: January 2021

Memory and forgetting constitute two sides of the same coin, and although the first has been extensively investigated, the latter is often overlooked. A possible approach to better understand forgetting is to develop phenomenological models that implement its putative mechanisms in the most elementary way possible, and then experimentally test the theoretical predictions of these models. One such mechanism proposed in previous studies is retrograde interference, stating that a memory can be erased due to subsequently acquired memories. In the current contribution, we hypothesize that retrograde erasure is controlled by the relevant “importance” measures such that more important memories eliminate less important ones acquired earlier. We show that some versions of the resulting mathematical model are broadly compatible with the previously reported power-law forgetting time course and match well the results of our recognition experiments with long, randomly assembled streams of words.
The National Immunization Technical Advisory Group in Israel
Authors: Stein-Zamir Chen , Rishpon Shmuel
Published: January 2021

National Immunization Technical Advisory Groups (NITAGs) are defined by the World Health Organization as multidisciplinary groups of health experts who are involved in the development of a national immunization policy. The NITAG has the responsibility to provide independent, evidence-informed advice to the policy makers and national programme managers, on policy issues and questions related to immunization and vaccines.

This paper aims to describe the NITAG in Israel. The Israeli NITAG was established by the Ministry of Health in1974. The NITAG’s full formal name is “the Advisory Committee on Infectious Diseases and Immunizations in Israel”. The NITAG is charged with prioritizing choices while granting maximal significance to the national public health considerations. Since 2007, the full minutes of the NITAG’s meetings have been publicly available on the committee’s website (at the Ministry of Health website, in Hebrew).

According to the National Health Insurance Law, all residents of Israel are entitled to receive universal health coverage. The health services basket includes routine childhood immunizations, as well as several adult and post - exposure vaccinations. The main challenge currently facing the NITAG is establishing a process for introducing new vaccines and updating the vaccination schedule through the annual update of the national health basket. In the context of the annual update, vaccines have to “compete” with multiple medications and technologies which are presented to the basket committee for inclusion in the national health basket. Over the years, the Israeli NITAG’s recommendations have proved essential for vaccine introduction and scheduling and for communicable diseases control on a national level. The NITAG has established structured and transparent working processes and a decision framework according to WHO standards, which is evidence-based and country-specific to Israel.

The recent global COVID-19 pandemic is a major concern for all countries as well as a challenge for NITAGs. Currently, the NITAGs have a key role in advising both on sustainment of the routine immunization programs and on planning of the COVID-19 vaccination campaigns, with ongoing updates and collaboration with the Ministry of Health and health organizations.
On continuity of the fractional derivative of the time-fractional semilinear pseudo-parabolic systems
Authors: Karapinar Erdal , Binh Ho Duy , Luc Nguyen Hoang , Can Nguyen Huu
Published: January 2021

In this work, we study an initial value problem for a system of nonlinear parabolic pseudo equations with Caputo fractional derivative. Here, we discuss the continuity which is related to a fractional order derivative. To overcome some of the difficulties of this problem, we need to evaluate the relevant quantities of the Mittag-Leffler function by constants independent of the derivative order. Moreover, we present an example to illustrate the theory.
Diterpenoids as potential anti-malarial compounds from Andrographis paniculata
Authors: Dwivedi Manish Kumar , Mishra Shringika , Sonter Shruti , Singh Prashant Kumar
Published: January 2021

Background

The objectives of the current study are to evaluate the traditionally used medicinal plantsAndrographis paniculatafor in vitro anti-malarial activity against human malarial parasitePlasmodium falciparumand to further characterize the anti-malarial active extract ofA. paniculatausing spectroscopic and chromatographic methods.

Results

The chloroform extract ofA. paniculatadisplayed anti-malarial activity with IC50values 6.36 μg/ml against 3D7 strain and 5.24 μg/ml against K1 strains respectively with no evidence of significant cytotoxicity against mammalian cell line (CC50> 100 μg/ml). LC-MS analysis of the extract led to the identification of 59 compounds based on their chromatographic and mass spectrometric features (a total of 35 compounds are present in positive ion and 24 compounds in negative ion mode). We have identified 5 flavonoids and 30 compounds as diterpenoids in positive ion mode, while in the negative mode all identified compounds were diterpenoids. Characterization of the most promising class of compound diterpenoids using HPLC-LC-ESI-MS/MS was also undertaken.

Conclusions

The in vitro results undoubtedly validate the traditional use ofA. paniculatafor the treatment of malaria. The results have led to the identification of diterpenoids from IGNTU_06 extract as potential anti-malarial compounds that need to be further purified and analyzed in anti-malarial drug development programs.

Graphical abstract
Isolation and optimized production of putative antimicrobial compounds from Egyptian soil isolate Streptomyces sp. MS. 10
Authors: Sebak Mohamed , Saafan Amal E. , Abdelghani Sameh , Bakeer Walid , Moawad Abeer S. , El-Gendy Ahmed O.
Published: January 2021

Background

The rapid spread of antibiotic resistance has increased research interest in the discovery of natural products, mainly from actinomycetes, which have been the primary source of antimicrobial compounds. This study aimed to isolate, characterize, and optimize the production of some of the bioactive compounds from bioactive soil actinomycetes.

Results

One promising soil actinomycete, which was molecularly identified as Streptomyces sp. and designated as Streptomyces sp. MS. 10, showed broad-spectrum antimicrobial activity, including activity against methicillin-resistant Staphylococcus aureus. Thus, it was selected for isolation of its major bioactive compounds. Polymerase chain reaction amplification of the genes responsible for antibiotic biosynthesis showed the presence of genes encoding type I and type II polyketide synthase. Liquid chromatography-mass spectrometry analysis found that the major antimicrobial compounds produced by Streptomyces sp. MS. 10 were weakly ionized bioactive secondary metabolites. A large-scale fermentation experiment of Streptomyces sp. MS. 10 using pre-optimized culture conditions followed by bioassay-guided chromatographic separation of its secondary metabolites resulted in the isolation of putative bioactive compounds that were identified as fatty acids using proton nuclear magnetic resonance spectroscopy.

Conclusions

Egyptian soil is still a good source for exploring bioactive actinomycetes. Additionally, this study highlighted the importance of combining both physicochemical and genotypic characterization with spectroscopic analysis of the major natural products when isolating bioactive metabolites.
Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update
Authors: Virgo Katherine S. , Rumble R. Bryan , de Wit Ronald , Mendelson David S. , Smith Thomas J. , Taplin Mary-Ellen , Wade James L. , Bennett Charles L. , Scher Howard I. , Nguyen Paul L. , Gleave Martin , Morgan Scott C. , Loblaw Andrew , Sachdev Sean , Graham David L. , Vapiwala Neha , Sion Amy M. , Simons Virgil H. , Talcott James
Published: January 2021

PURPOSE

Update all preceding ASCO guidelines on initial hormonal management of noncastrate advanced, recurrent, or metastatic prostate cancer.

METHODS

The Expert Panel based recommendations on a systematic literature review. Recommendations were approved by the Expert Panel and the ASCO Clinical Practice Guidelines Committee.

RESULTS

Four clinical practice guidelines, one clinical practice guidelines endorsement, 19 systematic reviews with or without meta-analyses, 47 phase III randomized controlled trials, nine cohort studies, and two review papers informed the guideline update.

RECOMMENDATIONS

Docetaxel, abiraterone, enzalutamide, or apalutamide, each when administered with androgen deprivation therapy (ADT), represent four separate standards of care for noncastrate metastatic prostate cancer. Currently, the use of any of these agents in any particular combination or series cannot be recommended. ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide should be offered to men with metastatic noncastrate prostate cancer, including those who received prior therapies, but have not yet progressed. The combination of ADT plus abiraterone and prednisolone should be considered for men with noncastrate locally advanced nonmetastatic prostate cancer who have undergone radiotherapy, rather than castration monotherapy. Immediate ADT may be offered to men who initially present with noncastrate locally advanced nonmetastatic disease who have not undergone previous local treatment and are unwilling or unable to undergo radiotherapy. Intermittent ADT may be offered to men with high-risk biochemically recurrent nonmetastatic prostate cancer. Active surveillance may be offered to men with low-risk biochemically recurrent nonmetastatic prostate cancer. The panel does not support use of either micronized abiraterone acetate or the 250 mg dose of abiraterone with a low-fat breakfast in the noncastrate setting at this time. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .
Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L
Authors: Lafontaine Nicole , Campbell Purdey J , Castillo-Fernandez Juan E , Mullin Shelby , Lim Ee Mun , Kendrew Phillip , Lewer Michelle , Brown Suzanne J , Huang Rae-Chi , Melton Phillip E , Mori Trevor A , Beilin Lawrence J , Dudbridge Frank , Spector Tim D , Wright Margaret J , Martin Nicholas G , McRae Allan F , Panicker Vijay , Zhu Gu , Walsh John P , Bell Jordana T , Wilson Scott G
Published: January 2021

Context

Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited.

Objective

To identify novel associations between fT3, fT4, and TSH and differentially methylated positions (DMPs) in the genome in subjects from 2 Australian cohorts.

Method

We performed an epigenome-wide association study (EWAS) of thyroid function parameters and DNAm using participants from: Brisbane Systems Genetics Study (median age 14.2 years, n = 563) and the Raine Study (median age 17.0 years, n = 863). Plasma fT3, fT4, and TSH were measured by immunoassay. DNAm levels in blood were assessed using Illumina HumanMethylation450 BeadChip arrays. Analyses employed generalized linear mixed models to test association between DNAm and thyroid function parameters. Data from the 2 cohorts were meta-analyzed.

Results

We identified 2 DMPs with epigenome-wide significant (P < 2.4E−7) associations with TSH and 6 with fT3, including cg00049440 in KLF9 (P = 2.88E−10) and cg04173586 in DOT1L (P = 2.09E−16), both genes known to be induced by fT3. All DMPs had a positive association between DNAm and TSH and a negative association between DNAm and fT3. There were no DMPs significantly associated with fT4. We identified 23 differentially methylated regions associated with fT3, fT4, or TSH.

Conclusions

This study has demonstrated associations between blood-based DNAm and both fT3 and TSH. This may provide insight into mechanisms underlying thyroid hormone action and/or pituitary-thyroid axis function.
The Relationship Between Glucose Control and Cognitive Function in People With Diabetes After a Lacunar Stroke
Authors: Cukierman-Yaffe Tali , McClure Leslie A , Risoli Thomas , Bosch Jackie , Sharma Mike , Gerstein Hertzel C , Benavente Oscar
Published: January 2021

Context

Lacunar strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c).

Objective

The aim of this study was to assess the relationship between A1c and cognitive function in lacunar stroke patients with diabetes.

Methods

The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306).

Results

Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, –0.101 to –0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, –0.0043 to –0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities.

Conclusion

This analysis of lacunar stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.
Update on Novel Hormonal and Nonhormonal Male Contraceptive Development
Authors: Long Jill E , Lee Min S , Blithe Diana L
Published: January 2021

Background

The advent of new methods of male contraception would increase contraceptive options for men and women and advance male contraceptive agency. Pharmaceutical R&D for male contraception has been dormant since the 1990s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports most ongoing hormonal male contraceptive development. Nonhormonal methods are in earlier stages of development.

Content

Several hormonal male contraceptive agents have entered clinical trials. Novel single agent products being evaluated include dimethandrolone undecanoate, 11β-methyl-nortestosterone dodecylcarbonate, and 7α-methyl-19-nortestosterone. A contraceptive efficacy trial of Nestorone®/testosterone gel is underway. Potential nonhormonal methods are at preclinical stages of development. Many nonhormonal male contraceptive targets that affect sperm production, sperm function, or sperm transport have been identified.

NICHD supports development of reversible male contraceptive agents. Other organizations such as the World Health Organization, the Population Council, and the Male Contraception Initiative are pursuing male contraceptive development, but industry involvement remains limited.
Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men
Authors: Kiya Mai , Tamura Yoshifumi , Takeno Kageumi , Someya Yuki , Kakehi Saori , Sato Motonori , Yamasaki Nozomu , Kadowaki Satoshi , Suzuki Ruriko , Furukawa Yasuhiko , Sugimoto Daisuke , Kaga Hideyoshi , Funayama Takashi , Nishitani-Yokoyama Miho , Shimada Kazunori , Daida Hiroyuki , Aoki Shigeki , Satoh Hiroaki , Kawamori Ryuzo , Watada Hirotaka
Published: January 2021

Context

Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians.

Design and Setting

To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups.

Results

The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups.

Conclusions

In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.
Impaired Immune Function in Patients With Chronic Postsurgical Hypoparathyroidism: Results of the EMPATHY Study
Authors: Puliani Giulia , Hasenmajer Valeria , Sciarra Francesca , Barbagallo Federica , Sbardella Emilia , Pofi Riccardo , Gianfrilli Daniele , Romagnoli Elisabetta , Venneri Mary Anna , Isidori Andrea M
Published: January 2021

Context

Despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism.

Objective

This work aimed to evaluate immune function in hypoparathyroidism.

Methods

The Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control, cross-sectional study set in an Italian referral center. Participants included 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measures included calcium metabolism assessment, peripheral blood mononuclear cells (PBMC) profiling via flow cytometry, parathyroid hormone receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time polymerase chain reaction, cytokine measurement, and evaluation of infectious disease frequency and severity.

Results

Immune cell profiling revealed decreased monocytes, regulatory, naive, and total CD4+ T lymphocytes, which correlated with total calcium, ionized calcium, and PTH levels, in patients with hypoparathyroidism. Patients with hypoparathyroidism had a higher CD3−CD56+ natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor gene expression and decreased circulating TNF levels. Gene expression and immunofluorescence analysis confirmed PTHr1 expression in all PBMC lineages; however, the percentage of cells expressing PTHr1 was lower, whereas the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8+CD4+ and CD4+ T lymphocytes, and total NK cells was higher in patients with hypoparathyroidism.

Conclusions

This study describes for the first time the immune alterations in patients with hypoparathyroidism receiving conventional therapies, supporting the immunoregulatory role of PTH and proposing an explanation for the increased susceptibility to infections observed in epidemiological studies.
The Development of Financial Economics in France between the Mid-1970s and the Early 1980s
Authors: Jovanovic Franck , Numa Guy
Published: January 2021

To date, little research has documented the international diffusion of financial economics. Financial economics was supposedly “introduced” in France in the 1970s. Some analysts have argued that it is an American author—Leonard J. Savage—who allowed French authors to rediscover Louis Bachelier’s work, indicating that “a prophet is not without honor, save in his own country.” The present article challenges this conventional narrative and studies for the first time how financial economics was disseminated in France between the mid-1970s and the early 1980s. It shows that, when financial economics was “imported” from the United States in France in 1970s, some pioneering French contributions have been taught for almost a century. Based on this result, the article explains why the French authors who disseminated these ideas rarely referred to the works of French forerunners. It also clarifies the role of the French economists in this process. All of this suggests that the “import” of financial economics in France was in fact a reintroduction.
U.S. Occupational Mobility of Children of Immigrants Based on Parents' Origin-Country Occupation
Authors: Potochnick Stephanie , Hall Matthew
Published: January 2021

This study provides a national-level assessment of occupational mobility and early-career attainment of children of immigrants based on parents' origin-country occupation. Exploiting unique aspects of the Educational Longitudinal Study, we examine how parent-child U.S. intergenerational occupational mobility patterns and child occupational attainment differ based on parental premigration occupational status (i.e., low- vs. high-skilled) and parental postmigration occupational mobility (i.e., upward, same, or downward). Our results suggest misestimation in intergenerational mobility research if parents' origin-country occupation is excluded. Including parents' origin-country occupation, we find that the children of immigrants are recovering from instances of parental occupational downgrading, building on parental advances, and advancing where parents could not. Furthermore, most children of immigrants do as well or better occupationally than children of non-Hispanic White natives. Strong educational investments help explain this advantage, particularly for children of high-skilled immigrants. However, results indicate that all children of immigrants would attain even more if they faced fewer postmigration barriers, especially children of low-skilled immigrants. These results advance immigrant selection and assimilation theories by demonstrating how pre- and postmigration factors influence occupational attainment of children of immigrants.
Taking the Long View: COVID-19 Priorities for the Biden Administration
Authors: Galea Sandro , Ettman Catherine K. , Maani Nason , Abdalla Salma M.
Published: January 2021

The COVID-19 pandemic transformed the American political landscape, influencing the course of the 2020 election and creating an urgent policy priority for the new administration. The Biden-Harris plan for beating COVID-19 represents a practicable, technically competent plan to contain the pandemic, one that will serve the country well in the months ahead. The authors suggest that the United States would also benefit from an even bolder set of aspirations—reframing the national conversation on COVID-19, embedding equity in all health decision making, strengthening the social safety net, and changing how we talk about health—as part of the national response to COVID-19. This would represent a genuine step forward in the US approach to health, informed by the systemic flaws COVID-19 exposed, and would realize benefits from the pandemic moment that in turn would propel national health forward for the rest of the century.
Prescription Drug Priorities under the Biden Administration
Authors: Gavulic Kyle A. , Dusetzina Stacie B.
Published: January 2021

In January 2021, the incoming Biden administration inherited urgent priorities for curbing health care spending and expanding health care coverage to millions of Americans while also addressing the COVID-19 pandemic and resulting economic downturn. Among these competing priorities is the issue of access to and affordability of prescription drugs. Here, the authors outline Biden's plan for directly lowering prescription drug spending for payers and patients and for expanding access to prescription medications through improved health insurance coverage. These policies could provide important financial protections for Americans against high prescription drug prices. Despite widespread public support for addressing prescription drug prices, many of Biden's plans rely on congressional action, which will be complicated by the narrow majority held by Democrats in the House and an evenly divided Senate. However, there may be other opportunities for reducing prescription drug spending and improving health insurance enrollment among the uninsured. While directly lowering drug prices would provide the most widespread savings for payers and patients alike, any successful effort for increasing the number of Americans enrolled in health insurance or rendering it more affordable will still likely effectively lower patients' out-of-pocket costs and improve access to prescription drugs.