bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital health for sexually transmitted infection and HIV services: a global scoping review
Authors: Cao Bolin , Bao Huanyu , Oppong Emmanuela , Feng Siyang , Smith Kumi M. , Tucker Joseph D. , Tang Weiming
Published: November 2019

Purpose of review

The current study aimed to review how digital health has been used for sexually transmitted infection (STI)/HIV prevention, testing, and treatment.

Recent findings

A scoping review was conducted by searching five databases for peer-reviewed literature published between March 2018 to August 2019. 23 out of 258 studies met the inclusion criteria and were assessed. Six studies used digital platform to enhance STI/HIV prevention messaging; four studies found that digital health can provide vivid promotional information and has been instrumental in increasing the accessibility and acceptability of STI/HIV testing; three studies reported digital health provides a channel to understand and interpret the discourses on preexposure prophylaxis (PrEP) and increase PrEP uptake; three studies focused on refining big data algorithms for surveillance; four studies reported on how digital interventions could be used to optimize clinical interventions; and four studies found digital interventions can be used to assist mental health services.

Digital health is a powerful and versatile tool that can be utilized in the production of high-quality, innovative strategies on STIs and HIV services. Future studies should consider focusing on strategies and implementations that leverage digital platforms for network-based interventions, in addition to recognizing the norms of individual digital intervention platforms.
Host–vaginal microbiota interactions in the pathogenesis of bacterial vaginosis
Authors: Muzny Christina A. , Łaniewski Paweł , Schwebke Jane R. , Herbst-Kralovetz Melissa M.
Published: November 2019

Purpose of review

The cause of bacterial vaginosis, the most common cause of vaginal discharge in women, remains controversial. We recently published an updated conceptual model on bacterial vaginosis pathogenesis, focusing on the roles of Gardnerella vaginalis and Prevotella bivia as early colonizers and Atopobium vaginae and other bacterial vaginosis-associated bacteria (BVAB) as secondary colonizers in this infection. In this article, we extend the description of our model to include a discussion on the role of host–vaginal microbiota interactions in bacterial vaginosis pathogenesis.

Recent findings

Although G. vaginalis and P. bivia are highly abundant in women with bacterial vaginosis, neither induce a robust inflammatory response from vaginal epithelial cells. These early colonizers may be evading the immune system while establishing the bacterial vaginosis biofilm. Secondary colonizers, including A. vaginae, Sneathia spp., and potentially other BVAB are more potent stimulators of the host–immune response to bacterial vaginosis and likely contribute to its signs and symptoms as well as its adverse outcomes.

Elucidating the cause of bacterial vaginosis has important implications for diagnosis and treatment. Our current bacterial vaginosis pathogenesis model provides a framework for key elements that should be considered when designing and testing novel bacterial vaginosis diagnostics and therapeutics.
Efficacy and Safety of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients
Authors: Yadav Madhav Prasad , Ballal Sanjana , Bal Chandrashekhar , Sahoo Ranjit Kumar , Damle Nishikant Avinash , Tripathi Madhavi , Seth Amlesh
Published: November 2019

Purpose

The aim of this study was to evaluate the efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC).

Methods

In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic 68Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent 177Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients.

Results

The median age of patients was 66.5 years (range, 30–88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects.

Conclusions

177Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.
Nuclear Medicine Student Elective at the Keck School of Medicine at LAC-USC Medical Center
Authors: Wassef Heidi R.
Published: November 2019

Very few medical schools offer a nuclear medicine elective. I will share our experience with the nuclear medicine elective rotation which has been well received by our fourth-year medical students. This may be of interest to nuclear medicine physicians who work in an academic setting.
Detection of Unusual Peritoneal Metastases of Prostate Cancer With 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Simsek Duygu Has , Sanli Yasemin
Published: November 2019

Peritoneal metastasis of prostate cancer (PC) is unusual site of metastatic disease; only limited case reports are published in literature. 68Ga–prostate-specific membrane antigen (PSMA) PET/CT is recently used for detection of PC metastasis with high accuracy rates. We present a case of a 68-year-old man with disseminated peritoneal metastases and abdominal metastatic lymph nodes of PC, demonstrated in 68Ga-PSMA PET/CT with intense PSMA uptake.
FDG PET Findings of Hyperprogression During Immunotherapy in a Patient With Hepatocellular Carcinoma
Authors: Wang Jingnan , Wang Xuezhu , Yang Xu , Zhao Haitao , Huo Li
Published: November 2019

Although immunotherapy is a successful approach in oncology, it might be detrimental to some patients. In the condition of hyperprogression, patients experience accelerated progression after immunotherapy, resulting in a worse outcome. Hyperprogression may be difficult to be identified in the early stage. Once the diagnosis is confirmed in the follow-up evaluation, the immunotherapy should be stopped immediately. In this case, we report a hyperprogression patient during combined immunotherapy toward metastatic hepatocellular carcinoma observed by serial 18F-FDG PET.
Retroperitoneal Liposarcoma on 99mTc-DTPA Renal Scintigraphy
Authors: Chen Haotian , Wei Jing , Wang Rang , Xiang Yongzhao , Fan Chengzhong
Published: November 2019

Retroperitoneal liposarcoma is usually large and can press on other organs. We report a case of a 66-year-old woman with a history of retroperitoneal liposarcoma resection who presented to the emergency department with abdominal pain. Ultrasonography revealed a large abdominal mass with renal displacement. Dynamic renal scintigraphy with 99mTc-DTPA was conducted to evaluate renal function. However, severe impairment of the right kidney function and abnormal tracer accumulation were observed during the examination. SPECT/CT was performed; 2 kidneys were successfully localized, and the recurrence of tumor was correctly detected.
A Novel Technique for Performing Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA): A Single-port Platform
Authors: Park Jung Ho , Bilegsaikhan Sanchir-Erdene , Suh Yong Joon
Published: November 2019

During transoral endoscopic thyroidectomy vestibular approach (TOETVA), the mental nerve can be injured by the lateral ports. Mental nerve injury is a worrisome complication, which can be minimized by using the single-port platform. A 56-year-old woman was diagnosed with a 5-mm sized papillary thyroid carcinoma on the isthmus. A horizontal 21-mm incision was made on the mucosa at the lower lip, followed by vertical dissection from the mentalis muscles down to the mandibular area. Subsequent hydrodissection widened the working space. For the single-port procedure, the KeyPort system was applied. After inserting the endoscopic instruments, the thyroid isthmus was resected as usual. The patient was discharged without any complications. To our knowledge, this is the first report of single-port TOETVA. Although the indications are limited, a single-port platform can be utilized for TOETVA. This will minimize the risk of mental nerve injury.
Cerebellar ataxias: an update
Authors: Manto Mario , Gandini Jordi , Feil Katharina , Strupp Michael
Published: November 2019

Purpose of review

Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum.

Recent findings

Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias.

Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.
Spaceflight associated neuro-ocular syndrome
Authors: Wojcik Peter , Kini Ashwini , Al Othman Bayan , Galdamez Laura A. , Lee Andrew G.
Published: November 2019

Purpose of review

Several decades of long duration space flight missions by the National Aeronautics and Space Administration has revealed an interesting and unique constellation of neuro-ophthalmic findings now called spaceflight associated neuro-ocular syndrome (SANS). The unique space environment of microgravity produces novel physiological changes and derangements that present a challenge to astronauts in current and future long duration space missions. Although the precise mechanism of SANS is not fully understood, in this review, we examine recent developments that may to help explain possible causes and potential countermeasures.

Recent findings

The cause of SANS is still largely unknown. A growing body of evidence implicates multiple factors that contribute to the development of SANS including cephalad fluid shifts, increased intracranial pressure, venous/lymphatic stasis, inflammation, metabolism, axoplasmic stasis and radiation exposure.

The pathologic mechanism behind SANS may be multifactorial and may be amenable to different countermeasures for prevention and management of SANS.
A Pilot Study Comparing Effects of Bifrontal Versus Bitemporal Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Mild Alzheimer Disease
Authors: Liu Celina S. , Herrmann Nathan , Gallagher Damien , Rajji Tarek K. , Kiss Alex , Vieira Danielle , Lanctôt Krista L.
Published: November 2019

Objective

While transcranial direct current stimulation (tDCS) can enhance aspects of memory in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), there has been wide variability in both the placement of tDCS electrodes and treatment response. This study compared the effects of bifrontal (anodal stimulation over the dorsolateral prefrontal cortices), bitemporal (anodal stimulation over the temporal cortices), and sham tDCS on cognitive performance in MCI and AD.

Methods

Seventeen patients diagnosed with MCI or mild AD received 3 sessions of anodal tDCS (bifrontal, bitemporal, 2 mA for 20 minutes; and sham) in random order. Sessions were separated by 1 week. The Alzheimer's Disease Assessment Scale–Cognitive Word Recognition Task, Alzheimer's Disease Assessment Scale–Cognitive Word Recall Task, 2-back, and Montreal Cognitive Assessment were used to assess cognition.

Results

There was a significant effect of stimulation condition on 2-back accuracy (F
2,28 = 5.28 P = 0.01, η2
p = 0.27), with greater improvements following bitemporal tDCS compared with both bifrontal and sham stimulations. There were no significant changes on other outcome measures following any stimulation. Adverse effects from stimulation were mild and temporary.

Conclusions

These findings demonstrate that improvements in specific memory tasks can be safely achieved after a single session of bitemporal tDCS in MCI and mild AD patients.
Torulaspora nypae sp. nov., a novel yeast species isolated from nipa (Nypa fruticans Wurmb.) inflorescence sap in southern Thailand
Authors: Kaewwichian Rungluk , Khunnamwong Pannida , Am-In Somjit , Jindamorakot Sasitorn , Limtong Savitree
Published: November 2019

Two strains (YSP-384 and YSP-399), representing a novel Torulaspora species, were isolated from two nipa inflorescence sap samples collected in Trang province in the southern part of Thailand. The two strains had identical sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions. The two strains were closest to Torulaspora maleeae CBS 10694T, but with 1.1 % nucleotide substitutions in the D1/D2 domains of the LSU rRNA gene and 5.2 % nucleotide substitutions in the ITS regions. Phylogenetic analysis based on the concatenated sequences of the ITS regions and the D1/D2 domains of the LSU rRNA gene supported that the two strains represented a distinct species in the genus Torulaspora. Some phenotypic characteristics of the two strains differed from T. maleeae including the two strains have ability to assimilate d-xylose, d-glucono-δ-lactone and melizitose, and inability to ferment maltose and raffinose, whereas T. maleeae has opposite results. Therefore, the two strains are described as representing a novel species, for which the name Torulaspora nypae sp. nov. was proposed.
Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment
Authors: Huang RunYue , Li Fang , Zhou Yingyan , Zeng Zhenhua , He Xiaohong , Fang Lihua , Pan Feng , Chen Yile , Lin Jiehua , Li Jie , Qiu Dongni , Tian Yinping , Tan Xi , Song Yanni , Xu Yongyue , Lai Yonghui , Yi Hao , Gao Qiang , Fang Xiaodong , Shi Mingming , Zhou Chu , Huang Jinqun , He Yi-Ting
Published: November 2019

Introduction. Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy.

Aim. We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients.

Methodology. Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen–Qiangdu–Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined.

Results. Four species were enriched in the patients with AS:

Flavonifractor plautii

,

Oscillibacter

,

Parabacteroides distasonis

and

Bacteroides nordii

(HC vs. NM, P<0.05); only

F. plautii

was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains.

F. plautii

was found to be significantly increased in the comparison between the HC and WM groups, along with four other species (

Clostridium bolteae

, Clostridiales bacterium 1_7_47FAA,

C. asparagiforme

and

C. hathewayi

). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins.

Conclusion. The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.
Role of the hippocampus during logical reasoning and belief bias in aging
Authors: Ziaei Maryam , Bonyadi Mohammad Reza , Reutens David C.
Published: November 2019

Reasoning requires initial encoding of the semantic association between premises or assumptions, retrieval of these semantic associations from memory, and recombination of information to draw a logical conclusion. Currently-held beliefs can interfere with the content of the assumptions if not congruent and inhibited. This study aimed to investigate the role of the hippocampus and hippocampal networks during logical reasoning tasks in which the congruence between currently-held beliefs and assumptions varies. Participants of younger and older age completed a series of syllogistic reasoning tasks in which two premises and one conclusion were presented and they were required to decide if the conclusion logically followed the premises. The belief load of premises was manipulated to be either congruent or incongruent with currently-held beliefs. Our whole-brain results showed that older adults recruited the hippocampus during the premise integration stage more than their younger counterparts. Functional connectivity using a hippocampal seed revealed that older, but not younger, adults recruited a hippocampal network that included anterior cingulate and inferior frontal regions when premises were believable. Importantly, this network contributed to better performance in believable inferences, only in older adults group. Further analyses suggested that, in older adults group, the integrity of the left cingulum bundle was associated with the higher correct rejection of believable premises more than unbelievable ones. Using multimodal imaging, this study highlights the importance of the hippocampus during premise integration and supports the compensatory role of the hippocampal network during a logical reasoning task among older adults.
Distinct transcriptional programs of SOX2 in different types of small cell lung cancers
Authors: Tenjin Yuki , Matsuura Kumi , Kudoh Shinji , Usuki Shingo , Yamada Tatsuya , Matsuo Akira , Sato Younosuke , Saito Haruki , Fujino Kosuke , Wakimoto Joeji , Ichimura Takaya , Kohrogi Hirotsugu , Sakagami Takuro , Niwa Hitoshi , Ito Takaaki
Published: November 2019

SOX2is an oncogene in human small cell lung cancer (SCLC), an aggressive neuroendocrine (NE) tumor. However, the roles of SOX2 in SCLC remain unclear, and strategies to selectively target SOX2 in SCLC cells have not yet been established. We herein demonstrated that SOX2 is involved in NE differentiation and tumorigenesis in cooperation with ASCL1, a lineage-specific transcriptional factor, in the classical subtype of SCLC cell lines. ASCL1 recruits SOX2, which promotes INSM1 expression. Precursor SCLC lesions were established inTrp53(-/-);CCSPrtTA; tetOCre; floxedRb1; floxedHes1mice, and the NE neoplasms induced were positive for Ascl1, Sox2, and Insm1. In contrast to the ASCL1-SOX2 signaling axis to control the SCLC phenotype in classical subtype SCLC, SOX2 targeted distinct genes, such as those related to the Hippo pathway, in ASCL1-negative, variant subtype SCLC. The present results support the importance of the ASCL1-SOX2 axis as a main subtype of SCLC, and suggest the therapeutic potential of targeting the ASCL1-SOX2 signaling axis and the clinical utility of SOX2 as a biological marker in the classical subtype of SCLC.
Two-way migration ofLychnis wilfordiicaused by the circular landform of Japan-Korea-northeast China-Russian Far East region and its suggestion for conservation in northeast Asia
Authors: Tamura Saya , Kwak Myounghai , Kokubugata Goro , Park Chan-ho , Lee Byoung-Yoon , Fukuda Tomoko , Petrunenko Ekaterina , Koksheeva Inna , Pimenova Elena , Krestov Pavel , Bondarchuk Svetlana , Ma Jin-Shuang , Zhou Hai-Cheng , Tsuboi Hayato , Nishikawa Yoko , Shimamura Takashi , Fujita Hiroko , Nakamura Koh
Published: November 2019

In northeast Asia, substantial portion of the floras, including endangered species, are shared among its component countries in the continental, peninsula, and island parts largely through Quaternary migration. To effectively conserve nationally endangered plants in Northeast Asia, transnational conservation studies are vitally needed.Lychnis wilfordii(Caryophyllaceae) has disjunct distribution in Russian Far East (Primorsky Krai), northeast China (Jilin), Korea (Gangwon-do) and Japan (Hokkaido, Aomori, Nagano), surrounding the sea, and this is designated as an endangered species in Japan and Korea. Population genetic and molecular dating analyses were conducted 1) to elucidate geographic genetic structure covering the species range, 2) to test possible scenarios of migration, and 3) to develop logical plans for effective conservation. Population genetic analyses indicated the continent and peninsula parts (north and south Primorsky Krai, Jilin, and Gangwon-do) had higher genetic diversity compared to those in the Japanese Archipelago (Hokkaido and Nagano). Five genetically distinct groups were recognized, namely, Nagano, Gangwon-do, Jilin, north and south Primorsky Krai plus Aomori, and Hokkaido. Genetic distance between Hokkaido and Nagano was larger than between Hokkaido and north Primorsky Krai, and between Nagano and Gangwon-do, crossing national borders and the natural barrier of the sea. Considering these results,L. wilfordiilikely migrated from the Asian continent to the Japanese Archipelago using two routes: north route from Russian Far East to Hokkaido and Aomori, and south route from the Korean Peninsula to Nagano. Based on molecular dating, migration from the continent to the islands likely occurred from the middle Pleistocene to the Holocene. For effective conservation ofL. wilfordii, Hokkaido and Nagano populations should be distinguished as different evolutionary significant units, although these two regions belong to the same country, because Hokkaido and Nagano populations are at the different ends of the two migratory routes based on the migration scenario.
Barking up the right tree: Univariate and multivariate fMRI analyses of homonym comprehension
Authors: Hoffman Paul , Tamm Andres
Published: November 2019

Homonyms are a critical test case for investigating how the brain resolves ambiguity in language and, more generally, how context influences semantic processing. Previous neuroimaging studies have associated processing of homonyms with greater engagement of regions involved in executive control of semantic processing. However, the precise role of these areas and the involvement of semantic representational regions in homonym comprehension remain elusive. We addressed this by combining univariate and multivariate fMRI analyses of homonym processing. We tested whether multi-voxel activation patterns could discriminate between presentations of the same homonym in different contexts (e.g.,barkfollowingtreevs.barkfollowingdog). The ventral anterior temporal lobe, implicated in semantic representation but not previously in homonym comprehension, showed this meaning-specific coding, despite not showing increased mean activation for homonyms. Within inferior frontal gyrus (IFG), a key site for semantic control, there was a dissociation between pars orbitalis, which also showed meaning-specific coding, and pars triangularis, which discriminated more generally between semantically related and unrelated word pairs. IFG effects were goal-dependent, only occurring when the task required semantic decisions, in line with a top-down control function. Finally, posterior middle temporal cortex showed a hybrid pattern of responses, supporting the idea that it acts as an interface between semantic representations and the control system. The study provides new evidence for context-dependent coding in the semantic system and clarifies the role of control regions in processing ambiguity. It also highlights the importance of combining univariate and multivariate neuroimaging data to fully elucidate the role of a brain region in semantic cognition.
The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor positive metastatic breast cancer
Authors: Wander Seth A. , Cohen Ofir , Gong Xueqian , Johnson Gabriela N. , Buendia-Buendia Jorge , Lloyd Maxwell R. , Kim Dewey , Luo Flora , Mao Pingping , Helvie Karla , Kowalski Kailey J. , Nayar Utthara , Waks Adrienne G. , Parsons Stephen , Martinez Ricardo , Litchfield Lacey M. , Ye Xiang S. , Yu Chun Ping , Jansen Valerie M. , Stille John R. , Smith Patricia S. , Oakley Gerard J. , Chu Quincy , Batist Gerald , Hughes Melissa , Kremer Jill D. , Garraway Levi A. , Winer Eric P. , Tolaney Sara M. , Lin Nancy U. , Buchanan Sean , Wagle Nikhil
Published: November 2019

Clinical resistance mechanisms to CDK4/6 inhibitors in HR+ breast cancer have not been clearly defined. Whole exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including RB1 loss, activating alterations in AKT1, RAS, AURKA, CCNE2, ERBB2, and FGFR2, and loss of ER expression. In vitro experiments confirmed that these alterations conferred CDK4/6i resistance. Cancer cells cultured to resistance with CDK4/6i also acquired RB1, KRAS, AURKA, or CCNE2 alterations, which conferred sensitivity to AURKA, ERK, or CHEK1 inhibition. Besides inactivation of RB1, which accounts for ∼5% of resistance, seven of these mechanisms have not been previously identified as clinical mediators of resistance to CDK4/6 inhibitors in patients. Three of these—RAS activation, AKT activation, and AURKA activation—have not to our knowledge been previously demonstrated preclinically. Together, these eight mechanisms were present in 80% of resistant tumors profiled and may define therapeutic opportunities in patients.

Significance

We identified eight distinct mechanisms of resistance to CDK4/6 inhibitors present in 80% of resistant tumors profiled. Most of these have a therapeutic strategy to overcome or prevent resistance in these tumors. Taken together, these findings have critical implications related to the potential utility of precision-based approaches to overcome resistance in many patients with HR+ MBC.
Kinetic control of stationary flux ratios for a wide range of biochemical processes
Authors: Mallory Joel D. , Kolomeisky Anatoly B. , Igoshin Oleg A.
Published: November 2019

One of the most intriguing features of biological systems is their ability to regulate the steady-state fluxes of the underlying biochemical reactions, however the regulatory mechanisms and their physicochemical properties are not fully understood. Fundamentally, flux regulation can be explained with a chemical kinetic formalism describing the transitions between discrete states with the reaction rates defined by an underlying free-energy landscape. Which features of the energy landscape affect the flux distribution? Here we prove that the ratios of the steady-state fluxes of quasi-first-order biochemical processes are invariant to energy perturbations of the discrete states and are only affected by the energy barriers. In other words, the non-equilibrium flux distribution is under kinetic and not thermodynamic control. We illustrate the generality of this result for three biological processes. For the network describing protein folding along competing pathways, the probabilities of proceeding via these pathways are shown to be invariant to the stability of the intermediates or to the presence of additional misfolded states. For the network describing protein synthesis, the error rate and the energy expenditure per peptide bond is proven to be independent of the stability of the intermediate states. For molecular motors such as myosin-V, the ratio of forward to backward steps and the number of ATP molecules hydrolyzed per step is demonstrated to be invariant to energy perturbations of the intermediate states. These findings place important constraints on the ability of mutations and drug perturbations to affect the steady-state flux distribution for a wide class of biological processes.
Enhancing stakeholder networks in wine tourism – evidence from Italian small municipalities
Authors: Festa Giuseppe , Shams S.M. Riad , Metallo Gerardino , Cuomo Maria Teresa
Published: November 2019

Purpose

The purpose of this paper is to explore validity and reliability of a possible collaboration model for wine tourism with a “public” basis, i.e. from the point of view of the municipality engaged in promoting the wine tourism industry insisting on the territory.

Design/methodology/approach

The survey, proposing a theoretical/empirical framework, has investigated, through an electronic platform, the municipalities belonging to the National Association of “Wine Cities.”

Findings

The research has demonstrated a substantial trustworthiness of the model, with further evidence about the underestimation of stakeholder networks on behalf of Italian small municipalities. A clear difference of perception between non-small municipalities and small municipalities has emerged with regard to the perceived relevance of the collaboration with the territorial wine tourism players/stakeholders.

Practical implications

A recent legislation in Italy, just focused on small municipalities, might help overcome these gaps, between non-small municipalities and small municipalities, releasing in the territories new energies for the development of wine tourism, from both planning and financing points of view.

Originality/value

Italy as country is the largest producer of wine in the world. Similarly, wine tourism, as additional wine business opportunity, is a successful phenomenon in Italy, even though with great margins of development (especially with comparison to the New World of Wine). One of the main limits of this delay is the lack of public-private collaboration, at widespread level, among the players/stakeholders of the sector. The model that has been proposed in this research contributes scientifically and practically to fill this gaps.
Heritage waste management
Authors: Shirvani Dastgerdi Ahmadreza , Stimilli Flavio , Pisano Carlo , Sargolini Massimo , De Luca Giuseppe
Published: November 2019

Purpose

The considerable volume of rubble generated by the 2016–2017 earthquakes in central Italy reveals a significant issue in the post-disaster reconstruction phase. Drawing from the experience of Macerata province and the city of Camerino, the purpose of this paper is to explore a possible change of attitude in the reuse of heritage waste materials in the reconstruction process of damaged historical villages and towns in Italy.

Design/methodology/approach

This research outlines a comparison between national and regional directives on the rubble management on the one hand, and the praxis on the other, carrying out semi-structured interviews with experts who have been involved in the reconstruction process of Macerata province and Camerino, in Marche region.

Findings

The research reveals that the current vision in Italy for the management of disaster waste is still very close to the traditional paradigm that gives heritage waste an intrinsic value, worthy of great efforts for its collection, catalogue and preservation in view of the likely philological restoration of the damaged heritage. The most recent experiences in Camerino show that institutions responsible for the conservation of cultural heritage may accept a possible paradigm shift towards a more innovative and less expert-driven approach to heritage waste materials and their possible upcycling.

Originality/value

Within a critique of the traditional restoration paradigm, this article links disaster waste management to the Sendai Framework for Disaster Risk Reduction, to enhance the long-term sustainability of historical villages and towns in Italy.
Intellectual capital and business performance: the role of dimensions of absorptive capacity
Authors: Ahmed Syed Saad , Guozhu Jia , Mubarik Shujaat , Khan Mumtaz , Khan Essa
Published: November 2019

Purpose

The purpose of this paper is to empirically examine the mediating role of potential and realized absorptive capacity in intellectual capital (IC) and business performance. It also investigates the direct impact of the components of IC on business performance.

Design/methodology/approach

Partial least square-structural equation modeling (PLS-SEM) was used to assess the effect of IC dimensions on performance and to analyze the mediating role of absorptive capacity in this relationship. Data were collected from 192 managers using a survey questionnaire with Likert scale items.

Findings

The findings of the study show that potential absorptive capacity does not intervene in the relationship between the components of IC and those of business performance. However, realized absorptive capacity, measured as the transformation and exploitation of knowledge, played a positive mediating role in the relationship between the dimensions of IC and those of business performance. Social capital was also noted as a weak predictor of business performance, while human capital and organizational capital had a profound positive influence.

Originality/value

This study contributes to the literature on IC by examining the role of realized and potential absorptive capacity in the relationship between IC components and firm performance. This research also helps practitioners recognize the importance of transformation and the exploitation of knowledge for business performance.
Effects of Halal social media and customer engagement on brand satisfaction of Muslim customer
Authors: Shah Syed Alamdar Ali , Sukmana Raditya , Fianto Bayu Arie , Ahmad Muhammad Ali , Usman Indrianawati Usman , Mallah Waqar Ahmed
Published: November 2019

Purpose

The purpose of this research is to examine the factors that affect brand satisfaction of a Muslim customer who is making purchases from selling outlets on social media.

Design/methodology/approach

The study used a new mechanism of sampling for research studies relating to social media which. Further, we used hierarchical regression to analyze the moderation effects of religiosity.

Findings

The authors’ findings suggest that religiosity has moderation effects on the relationship between halal social media and brand satisfaction of a Muslim customer and even higher moderation effects on relationship between customer engagement and brand satisfaction of a Muslim customer.

Research limitations/implications

The respondents of this research are completely unknown as the data has been collected from google-docs link sharing arrangement.

Practical implications

This study identifies factors that need to be focused on winning the brand loyalty of a Muslim customer.

Originality/value

This study provides a new sampling methodology to be used for the purpose of studies related to social media, which has been labeled as “social-media disguised snow ball sampling”. Further, this study is one of the few studies in the area of “halal social media”.
Spirituality at work and organizational commitment as moderating variables in relationship between Islamic spirituality and OCB IP and influence toward employee performance
Authors: Sani Achmad , Maharani Ekowati Vivin
Published: November 2019

Purpose

The purpose of this study is to analyze the influence of Islamic spirituality toward organizational citizenship behavior from Islamic perspective (OCBIP), influence Islamic spirituality toward OCBIP in which spirituality at work and organizational commitment become mediators and influence of OCBIP toward working performance.

Design/methodology/approach

The study was categorized as an explanatory research. The setting of the study was the branch office of BRI Syariah in Malang. The population was employees of the branch office. The samples were 217 employees of BRI Syariah Malang. With an estimated population of 193 individuals and a 5 per cent confidence level, the total samples were 150 employees, including the supervisors. The sampling technique was proportional random sampling, in which all members of the population have an equal chance to become a sample based on proportion per section (Sekaran, 2003). The data were primary data obtained through questionnaires. The questionnaire consisted of question items on Islamic spirituality, workplace spirituality, organizational commitment and OCBIP. The data analysis technique was partial least squares (PLS).

Findings

Islamic spirituality is not directly influencing toward OCBIP, spirituality at work and organizational commitment as moderation variables in the influence of Islamic spirituality toward OCB IP, OCBIP had influence toward working performance. Higher OCBIP would result in better working performance accepted, and at the opposite, lower OCBIP would result in poorer working performance.

Originality/value

There are some limitations of previous studies that examine spirituality relationships with OCB. Nasrudin et al. (2013) and Kazemipour et al. (2012) found significant correlations between spirituality with OCB, but there is an inconsistency of research findings to suggest that spirituality has no direct effect on OCB, but through individual perceptions of organization. As the study of spirituality with OCB is still limited, this study attempts to explain OCB from an Islamic perspective, to propose a framework on Islamic spirituality, spirituality at work as an individual source of OCB and moderation of organizational commitment using Djafri and Noordin’s (2017) and previous empirical studies, with an aim to integrate the spirituality and OCB in a model that can be used to better understand OCB. It is hoped that this model development will reduce the scarcity of literature on spirituality with OCB through organizational commitment. This will help the organization to understand the role of spirituality and organizational commitment to improve OCB of employees that ultimately will improve organizational performance.
Dynamical and optimal procedure to analyze the attributes of yield exhibiting material with double diffusion theories
Authors: Sohail Muhammad , Tariq Sana
Published: November 2019

Purpose

Thermal and species transport of magneto hydrodynamic Casson liquid over a stretched surface is investigated theoretically in this examination for the three-dimensional boundary layer flow of a yield exhibiting material. The phenomenon of heat and species relocation is based upon modified Fourier and Fick’s laws that involves the relaxation times for the transportation of heat and mass. Conservation laws are modeled under boundary layer analysis in the Cartesian coordinates system. The purpose of this paper is to find the influence of different emerging parameters on fluid velocity, temperature and transport of species.

Design/methodology/approach

Reconstructed nonlinear boundary layer ordinary differential equations are analyzed through eigenvalues and eigenvectors. Due to the complexity and non-existence of the exact solution of the transformed equations, a convergent series solution by the homotopy algorithm is also derived. The reliability of the applied scheme is presented by comparing the obtained results with the previous findings.

Findings

Physical quantities of interest are displayed through graphs and tables and discussed for sundry variables. It is discerned that higher magnetic influence slows down fluid motion, whereas concentration and temperature profiles upsurge. Reliability of the recommended scheme is monitored by comparing the obtained results for the dimensionless stress as a limiting case of previous findings and an excellent agreement is observed. Higher values of Schmidt number reduce the concentration profile, whereas mounting the values of Prandtl number reduces the dimensionless temperature field. Moreover, heat and species transfer rates increase by mounting the values of thermal and concentration relaxation times.

Originality/value

The phenomenon of heat and species relocation is based upon modified Fourier and Fick’s laws which involves the relaxation times for the transportation of heat and mass. Conservation laws are modeled under boundary layer analysis in the Cartesian coordinates system.
Business model transfer mechanism
Authors: Li Zhigang , He Shining , Ning Jing , Liu Zhen , Zhang Jingwei , Du Xin
Published: November 2019

Purpose

Starting from corporate entrepreneurship, spin-off entrepreneurship and business model theory, this paper aims to examine the key influential factors and inherent mechanism in the process of business model transfer from parent enterprise to spin-off start-ups.

Design/methodology/approach

Grounded theory method is fit for constructing theoretical models, which can discover and interpret phenomenon and activities. According to the guidance of theoretical sampling and other core principles in grounded theory, this study extracts two parent enterprises named Haier and Phnix and lots of spin-offs derived from them.

Findings

This paper presents the theoretical framework that business models transfer from parents to spin-offs and probes into the embedding logic and connection relationship between factors and categories in this process, such as preconditions, incubation veins, business model elements, stripping mechanism and independent operations.

Research limitations/implications

Although this study is focused on the manufacturing industry, the main characteristics, comparative advantages, governance rules summarized from transfer activities of business model in spin-off entrepreneurship can also bring inspirations to both parent enterprises and spin-off start-ups.

Originality/value

Excavates process and mechanism of business model transfer from internal to external, extends the theoretical perspectives about existing related theories such as corporate entrepreneurship, spin-off entrepreneurship and business model theory and reveals new approaches and methods on business model design, which is different from the past way.
Discussing the elephant in the room: the Republican Party and race issues
Authors: Pearcy Mark , Clabough Jeremiah
Published: November 2019

Purpose

The purpose of this paper is to explore the subtle racist rhetoric used by members of the Republican Party over the last 60 years connected to issues of race. The authors start by providing a brief history of the Republican Party and race issues. Then, the authors discuss the civic thinking skills stressed within the C3 Framework, specifically the ability to analyze politicians’ arguments. Then, the focus shifts to look at the racial literacy framework discussed by King et al. Finally, three activities are provided that enable students to grasp the subtle racist rhetoric used by some Republicans connected to issues of race.

Design/methodology/approach

In this paper, the authors explore race issues with members of the modern Republican Party. The authors design three classroom-ready activities by drawing on the best teaching practices advocated for in the C3 Framework. To elaborate, these activities allow students to research and analyze arguments made by some Republican politicians. This enables students to engage in the four dimensions of the Inquiry Arc in the C3 Framework.

Findings

The authors provide three activities that can be utilized in the high school social studies classroom to enable students to dissect American politicians’ messages connected to race issues. These activities can be adapted and utilized to enable students to examine a political candidate’s messages, especially those that contain subtle racist rhetoric. By completing the steps of these three activities, students are better prepared to be critical consumers of political messages and to hold elected officials accountable for their words, policies and actions.

Originality/value

In this paper, the authors explore the role of racist political rhetoric employed by members of the Republican Party over the last 60 years. The authors use the racial literacy framework advocated for by King et al. in three classroom-ready activities. The three activities are provided to help students break down the racist political rhetoric employed by notable members of the Republican Party.
Using found poetry to cultivate student literacy, empathy, and creativity
Authors: Johnson Jennifer
Published: November 2019

Purpose

The emphasis on primary sources and disciplinary literacy skills in not only the Common Core State Standards, but other national curricula (i.e. College Board exams and the NCSS C3 Framework) requires that teachers continue to find ways to integrate these skills into their elementary and secondary classrooms. The paper aims to discuss this issue.

Design/methodology/approach

This paper introduces a cross-disciplinary approach that integrates primary source reading skills and the arts to cultivate student literacy and creativity though the writing of found poems.

Findings

Found poetry activities based on social studies primary sources allow students to practice literacy skills, engage more deeply with social studies content, and also may encourage the development of historical empathy toward the experiences and perspectives of distant peoples and events.

Practical implications

After reading and analyzing primary sources, students can create and present their found poems in diverse formats which allows for student expression and creativity in the classroom. Teachers can easily modify found poetry activities to meet the needs of diverse learners.

Originality/value

This paper fulfills the identified need to increase literacy skills and incorporate more student participation in the classroom. Using the strategy of student-inspired found poems, primary sources become more tangible and meaningful to students. Found poems offer yet another way to integrate the arts into social studies education.