bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and Benefit of Cognitive Behavioural Therapy for Psychosis via Teleconsultation in Indonesia: A Case Study of a 40-Year-Old Schizoaffective Disorder Patient
Authors: Sutjiono Bianca , Ahmad Shafira Fawzia , Jaya Edo S.
Published: July 2022

Whilst Cognitive Behavioural Therapy for Psychosis (CBTp) has been found to reduce psychotic symptoms, most evidence supporting its implementation originates from studies in Western and high-income countries. Furthermore, questions remain regarding the efficacy of CBTp conducted via teleconsultation. Herein we report an ongoing case in Indonesia involving an individual with schizoaffective disorder, who received 60 sessions of CBTp over seven months. Sessions were delivered via a combination of voice and video calls. The patient, a 40-year-old male, was diagnosed with schizoaffective disorder at the age of 26. He exhibited symptoms of paranoid and religious delusions, hallucinations (auditory, visual, and somatic) and disorganised speech during our intake interview. Negative symptoms were not apparent. In the 14 years prior to our initial consultation, the patient was prescribed antipsychotics and demonstrated good adherence. He had no history of psychotherapy independent of our clinic. Treatment involved CBTp techniques, including psychoeducation, a symptom diary, relaxation, and behavioural experiments. Study outcome was assessed with Psychotic Symptom Rating Scales. Both hallucination and delusion subscale scores improved 53% from 53 at intake to 25 during an assessment administered 6 months later. Results from this study demonstrate that the CBTp is both feasible, and beneficial, when conducted via teleconsultation in Indonesia.
Does biotech education need new teaching methodologies?
Authors: Danies Giovanna
Published: July 2022

Biotechnology has the potential to solve some of the biggest problems that contribute to local and global inequalities. Thus, it is imperative to increase the participation of diverse communities in the development, implementation and adoption of biotechnology. Biotechnology has been applied as long as we have domesticated plants and animals, produced cheese, yogurt, bread and alcoholic drinks. Today, it is being used in numerous disciplines including medicine, bioremediation, agriculture, energy and material production. Artists and designers have had a role in challenging research and its societal questions. Education must prepare individuals for a future of complex challenges providing creative problem-solving and critical thinking skill as well as the ability to innovate in a technology-driven world. Furthermore, teacher pedagogies should allow students and teachers to critically debate the political, ethical and social issues from the practice of biotechnology. This question invites a wide range of research contributions in which we identify, evaluate and speculate on the role that multidisciplinary education has on the future of biotech. We invite both experimental works on the latest methodologies in this area but also critique and reflection beyond the ‘hype’ of these, potentially transformative pedagogical approaches.
Hong Kong wives say no to a big family—educational pairings and fertility in Hong Kong
Authors: Sun Skylar Biyang , Zhao Xiaohang
Published: July 2022

We used the 2016 Hong Kong Census data and the diagonal reference model to investigate the effects of partners' educational pairings on fertility in Hong Kong. Our findings suggest a negative relationship between couples' educational achievements and their fertility. Moreover, males' educational attainment is more consequential of whether having children or not and both males' and females' educational attainments are determinants of the number of children to raise. In addition, the more educated a wife is relative to her husband, the less likely the couple is to have children. Once these educationally hypogamous couples have at least one child, they tend to have fewer children than their homogamous counterparts. By contrast, couples with a relatively more educated male are more likely to have children and tend to rear more children than those in educationally homogamous marriages.
Flow in additively manufactured super-rough channels
Authors: Altland Samuel , Zhu Xiaowei , McClain Stephen , Kunz Robert , Yang Xiang
Published: July 2022

Metal additive manufacturing has enabled geometrically complex internal cooling channels for turbine and heat exchanger applications, but the process gives rise to large-scale roughness whose size is comparable to the channel height (which is 500

$\mathrm {\mu }$

m). These super-rough channels pose previously unseen challenges for experimental measurements, data interpretation and roughness modelling. First, it is not clear if measurements at a particular streamwise and spanwise location still provide accurate representation of the mean (time- and plane-averaged) flow. Second, we do not know if the logarithmic layer survives. Third, it is unknown how well previously developed rough-wall models work for these large-scale roughnesses. To answer the above practical questions, we conduct direct numerical simulations of flow in additively manufactured super-rough channels. Three rough surfaces are considered, all of which are obtained from computed tomography scans of additively manufactured surfaces. The roughness’ trough to peak sizes are 0.1

$h$

, 0.3

$h$

and 0.8

$h$

, respectively, where

$h$

is the intended half-channel height. Each rough surface is placed opposite a smooth wall and the other two rough surfaces, leading to six rough-wall channel configurations. Two Reynolds numbers are considered, namely

$Re_\tau =180$

and

$Re_\tau =395$

. We show first that measurements at one streamwise and spanwise location are insufficient due to strong mean flow inhomogeneity across the entire channel, second that the logarithmic law of the wall survives despite the mean flow inhomogeneity and third that the established roughness sheltering model remains accurate.
INTRODUCTIONDisrupting the Status Quo:Building Equitable Access to HIV PrEP in the US through Innovative Financing
Authors: Johnson Jeremiah , Killelea Amy , Dangerfield Derek T. , Beyrer Chris , Sharfstein Joshua M.
Published: July 2022

This special edition ofJLMEcenters on a novel proposal for a national PrEP access program with the potential to break through a failed status quo.
From COVID Vaccines to HIV Prevention:Pharmaceutical Financing and Distribution for the Public’s Health
Authors: Sharfstein Joshua M. , Conti Rena M. , Gee Rebekah E.
Published: July 2022

The complexity and inefficiency of the U.S. health care system complicates the distribution of life-saving medical technologies. When the public health is at stake, however, there are alternatives. The proposal for a national PrEP program published in this issue of the Journal applies some of the lessons of the national COVID vaccine campaign to HIV prevention. In doing so, it draws on other examples of public health approaches to the financing of medical technology, from vaccines for children to hepatitis C treatment.
Opportunities and Challenges of Generic Pre-Exposure Prophylaxis Drugs for HIV
Authors: Ballreich Jeromie , Levengood Timothy , Conti Rena M.
Published: July 2022

Antiretroviral pre-exposure prophylaxis (PrEP) is protective against HIV. Low utilization rates amongst HIV vulnerable populations are due in part to the high cost of PrEP. Generic PrEP offers the potential to improve health at significantly reduced costs. In this study, we examine early utilization patterns and prices for generic PrEP. We discuss the opportunities and challenges for generic PrEP to improve health among HIV vulnerable populations.
The Downstream Impacts of High Drug Costs for PrEP Have Hindered the Promise of HIV Prevention
Authors: Farrow Kenyon
Published: July 2022

Prior to the recent introduction of generic TDF/FTC in the U.S., access to pre-exposure prophylaxis (PrEP) for HIV was greatly limited due to the downstream effects of the high cost of the medication. This article argues that despite drug copay cards and patient assistance programs, the promise of drastically reduced HIV diagnoses has never been fully realized, and more policy reforms on drug pricing are needed to make ending the HIV epidemic a reality.
Normal Jews?
Authors: Stavans Ilan
Published: July 2022

This essay reviews the following works:

Migrations: Poem, 1976–2020. By Gloria Gervitz. Translated from the Spanish by Mark Schafer. New York: New York Review Books, 2021. Pp. 304. $20.00 paperback. ISBN: 9781681375700.

Polacos in Argentina: Polish Jews, Interwar Migration, and the Emergence of Transatlantic Jewish Culture. By Mariusz Kałczewiak. Tuscaloosa: University of Alabama Press, 2020. Pp. viii + 320. $49.95 hardcover. ISBN: 9780817320393.

The Other/Argentina: Jews, Gender, and Sexuality in the Making of a Modern Nation. By Amy K. Kaminsky. Albany: State University of New York Press, 2021. Pp. xviii + 262. $95.00 hardcover. ISBN: 9781438483290.

Competing Germanies: Nazi, Antifascist, and Jewish Theater in German Argentina, 1933–1965. By Robert Kelz. Ithaca, NY: Cornell University Press, 2020. Pp. 372. $25.95 paperback. ISBN: 9781501739866.

Nuestra América: My Family in the Vertigo of Translation. By Claudio Lomnitz. New York: Other Press, 2021. Pp. 464. $27.99 hardcover. ISBN: 9781635420708.

Nuestra América: Utopía y persistencia de una familia judía. By Claudio Lomnitz. Mexico City: Fondo de Cultura Económica, 2018. Pp. 336. $14.00 paperback. ISBN: 9786071660084.

Revolutionary Visions: Jewish Life and Politics in Latin American Film. By Stephanie M. Pridgeon. Toronto: University of Toronto Press, 2020. Pp. ix + 208. $50.00 hardcover. ISBN: 9781487508142.

Armed Jews in the Americas. Edited by Raanan Rein and David M. K. Sheinin. Leiden: E. J. Brill, 2021. Pp. 264. $142.00 hardcover. ISBN: 9789004462533.

Family Papers: A Sephardic Journey through the Twentieth Century. By Sarah Abrevaya Stein. New York: Farrar, Straus and Giroux, 2019. Pp. vi + 336. $28.00 hardcover. ISBN: 9780374185428.

La vocación desmesurada: Una biografía de Alberto Gerchunoff. By Mónica Szurmuk. Buenos Aires: Sudamericana Editorial, 2018. Pp. 431. $23.54 paperback. ISBN: 9789500761482.

Portrayals of Jews in Contemporary Argentine Cinema: Rethinking Argentinidad. By Mirna Vohnsen. Suffolk: Tamesis Books, 2019. Pp. 205. $99.00 hardcover. ISBN: 9781855663374.
The green lacewingChrysopa formosaas a potential biocontrol agent for managingSpodoptera frugiperdaandSpodoptera litura
Authors: Li Yu-Yan , Wang Ya-Nan , Zhang Hong-Zhi , Zhang Mao-Sen , Wang Meng-Qing , Mao Jian-Jun , Zhang Li-Sheng
Published: July 2022

Understanding predator–prey interactions is essential for successful pest management by using predators, especially for the suppression of novel invasive pest. The green lacewingChrysopa formosais a promising polyphagous predator that is widely used in the biocontrol of various pests in China, but information on the control efficiency of this predator against the seriously invasive pestSpodoptera frugiperdaand nativeSpodoptera liturais limited. Here we evaluated the predation efficiency ofC.formosaadults on eggs and first- to third-instar larvae ofS.frugiperdaandS.liturathrough functional response experiments and determined the consumption capacity and prey preference of this chrysopid. Adults ofC.formosahad a high consumption of eggs and earlier instar larvae of both prey species, and displayed a type II functional response on all prey stages. Attack rates of the chrysopid on different prey stages were statistically similar, but the handling time increased notably as the prey developed. The highest predation efficiency and shortest-handling time were observed forC.formosafeeding onSpodopteraeggs, followed by the first-instar larvae.C.formosaexhibited a significant preference forS.lituraoverS.frugiperdain a two-prey system. In addition, we summarized the functional response and predation efficiency of several chrysopids against noctuid pests and made a comparison with the results obtained fromC.formosa. These results indicate thatC.formosahas potential as an agent for biological control of noctuid pests, particularly for the newly invasive pestS.frugiperdain China.
Shutdown: How Covid Shook the World's Economy
Authors: Fredona Robert
Published: July 2022

“At the expense of anything?” rejoined Lady Carbury with energy. “One cannot measure such men by the ordinary rule.”

—Anthony Trollope, The Way We Live Now (1875)

Facile criticisms of Adam Tooze's new book, Shutdown: How Covid Shook the World's Economy, present themselves at once. It suffers by comparison to Tooze's masterpiece, The Wages of Destruction (2006)—easily one of the best historical works of the last two decades, a huge and original take on the economy of Nazi Germany, its geopolitics and political economy alike forged in reaction to the example of Fordist America, its war aims destined to fail because of an increasing deficit in the “balance of resources” vis-à-vis the Allies.
Entrepreneurship in Emerging Markets: Female Entrepreneurs in Colombia since 1990
Authors: Dávila Carlos , Lluch Andrea
Published: July 2022

This article analyzes changes in the composition of Colombia's entrepreneurial class since the 1990s. We identify an increasing heterogeneity among the country's entrepreneurs, marked by greater diversity in gender, social class, and educational level. We also note more diverse regional origins, career trajectories, and political orientations among this group. The increasing number of women entrepreneurs, especially, played a significant role in changing the dynamics of entrepreneurship within the country. To provide some examples, this article looks at the trajectories and career dynamics of a selected group of women business leaders in Colombia. In terms of conceptual framing, this article makes use of the alternative business history (ABH) approach developed to explore emerging markets.
Verrucariaceae from Nepal
Authors: Orange Alan , Chhetri Som G.
Published: July 2022

Twenty-eight species of Verrucariaceae are reported from Nepal. One genus and nine species are described as new: Nesothele gen. nov., sister to Staurothele s. lat., with a crustose to squamulose thallus, hymenial algae and 4–8 colourless muriform ascospores per ascus; Nesothele glebulosa sp. nov., resembling N. rugulosa but with smaller perithecia; Thelidium uvidulum sp. nov., producing a thin thallus with soralia, prominent perithecia, and 1-septate ascospores; Verrucaria antepotens sp. nov., having a well-developed thallus with dark-sided areoles, immersed perithecia, and small ascospores 12.5–16.5 μm long; V. lactea sp. nov., resembling V. praetermissa but with larger ascospores and a strongly deviating ITS sequence; V. parvipeltata sp. nov., with brown, basally constricted areoles on an extensive dark prothallus; V. senta sp. nov., with a brown cracked thallus and prominent naked perithecia; Willeya eminens sp. nov., with prominent perithecia, and differing from W. protrudens in its ITS sequence; W. irrigata sp. nov. with a thallus cracked into dark-sided areoles, and relatively large ascospores 28.5–40 μm long; W. nepalensis sp. nov. with a cracked thallus, immersed perithecia and a distinctive ITS sequence. Three species complexes might contain new taxa, but wider geographical sampling is necessary before delimiting species: Thelidium minutulum, Verrucaria elaeomelaena and V. hydrophila. Five new combinations are made: Willeya honghensis comb. nov. (for Staurothele honghensis), Nesothele globosa comb. nov. (for Endocarpon globosum), N. hymenogonia comb. nov. (for Staurothele hymenogonia), N. rugulosa comb. nov. (for Staurothele rugulosa) and N. succedens comb. nov. (for Staurothele succedens). Four species are unidentified.
Brazilian Veneto (Talian)
Authors: Guzzo Natália Brambatti
Published: July 2022

Brazilian Veneto is a Romance language spoken by approximately 500,000 people, most of whom live in the southern Brazilian states of Rio Grande do Sul, Santa Catarina and Paraná (Margotti 2004, Pereira 2017). It is also spoken in the southeastern Brazilian states of São Paulo and Espírito Santo (see e.g. Loriato 2019). The language is often referred to by its speakers as Talian (/taˈljaŋ/), meaning ‘Italian’, given the geographical origin of the speakers who developed it, even though it is not a variety of Standard Italian. In this Illustration, I will refer to the language under examination as Talian, following many speakers’ naming preference.
The judicial assessment of states’ action on climate change mitigation
Authors: Mayer Benoit
Published: July 2022

The Supreme Court of the Netherlands construed the state’s positive human rights obligations as requiring a 25 per cent reduction of its greenhouse gas emissions by 2020 compared with 1990 levels. This article explores how judges can decide the level of state effort required to mitigate climate change. To date, judges have predominantly approached this issue by seeking to identify an elusive benchmark, either by deduction from global objectives or induction from state conduct. This article shows that the judicial assessment of a state’s requisite efforts inevitably relies on equity infra legem. Acknowledging this, judges could learn from the international courts’ experience with establishing clarity in the midst of vague legal rules.
Organ Trafficking: Why Do Healthcare Workers Engage in It?
Authors: Stammers Trevor
Published: July 2022

Organ trafficking in all its various forms is an international crime which could be entirely eliminated if healthcare professionals refused to participate in or be complicit with it. Types of organ trafficking are defined and principal international declarations and resolutions concerning it are discussed. The evidence for the involvement of healthcare professionals is illustrated with examples from South Africa and China. The ways in which healthcare professionals directly or indirectly perpetuate illegal organ transplantation are then considered, including lack of awareness, the paucity of both undergraduate and postgraduate education on organ trafficking, turning a blind eye, advocacy of organ commercialism, and the lure of financial gain.
Full Reciprocity: An Essential Element for a Fair Opt-Out Organ Transplantation Policy
Authors: Fleck Leonard
Published: July 2022

In this paper, I argue for the following points. First, all of us have a presumptive moral obligation to be organ donors if we are in the relevant medical circumstances at the time of death. Second, family members should not have the right to interfere with the fulfillment of that obligation. Third, the ethical basis for that obligation is reciprocity. If we want a sufficient number of organs available for transplantation, then all must be willing donors. Fourth, that likelihood is diminished if individuals are entirely free to refuse to be organ donors but still would demand to be organ recipients. Fifth, although individuals would be ethically obligated to be organ donors, we still need to permit them to refuse to be organ donors. Sixth, to encourage individuals to stay within the organ donation system, we should have as a just and ethically justified policy denying individuals an organ transplant in the relevant medical circumstances if they have chosen to exit the organ donation system. Individuals would not be permitted to be organ recipients if they were unwilling to be organ donors. This is what it means to be part of what Rawls in Political liberalism (15-22) would refer to as a “fair system of social cooperation.” We refer to this as the “reciprocity requirement.”
The Duty to Protect, Abortion, and Organ Donation
Authors: Carroll Emily , Crutchfield Parker
Published: July 2022

Some people oppose abortion on the grounds that fetuses have full moral status and thus a right to not be killed. We argue that special obligations that hold between mother and fetus also hold between parents and their children. We argue that if these special obligations necessitate the sacrifice of bodily autonomy in the case of abortion, then they also necessitate the sacrifice of bodily autonomy in the case of organ donation. If we accept the argument that it is obligatory to override a woman’s bodily autonomy for the sake of an unborn child’s survival, we must continue to override the bodily autonomy of parents to ensure the survival of their living children, until the parent no longer has a special obligation to their child to the same degree as their special obligation to the fetus. And if the life of a child is truly more important than the bodily autonomy of its parents, as must be the case to force women to carry unwanted pregnancies to term, this should remain true until such a time that their children are no longer considered their responsibility. Thus, parity of reasoning suggests that policies compelling the gestation of a fetus should be accompanied by policies compelling organ donation.
Altruistic Organ Donation: On Giving a Kidney to a Stranger
Authors: Fleck Leonard , Ward Arthur
Published: July 2022

In the following interview, philosophers Leonard Fleck and Arthur Ward discuss the latter’s recent experience of being a nondirected kidney donor. The interview took place in the Center for Bioethics and Social Justice at Michigan State University.
Palliative stenting of the venous duct in a premature neonate with obstructed infradiaphragmatic total anomalous pulmonary venous connection
Authors: George Renelle S. , Lozier John S. , Bocks Martin L.
Published: July 2022

In infracardiac, infradiaphragmatic total anomalous pulmonary venous connection, all four pulmonary veins connect to a descending vertical vein that usually drains to the portal vein or one of its tributaries. Obstruction is common, and definitive treatment is surgical repair. We present a case of late-diagnosed infradiaphragmatic total anomalous pulmonary venous connection in a premature neonate who was too high risk for surgery and underwent palliative stenting of the venous duct. We demonstrate the feasibility of a transhepatic approach when umbilical access is no longer available.
China on display: the architecture of the Chinese pavilion at the 1904 Louisiana Purchase Exposition
Authors: Xie Yinrui
Published: July 2022

After the Boxer Rebellion ended with China’s crushing defeat and the signing of the Boxer Protocol, China participated in the 1904 Louisiana Purchase Exposition as its official debut at world’s fairs. The Chinese pavilion was supposed to represent the country’s national pride and cultural identity, yet ironically, the pavilion materialised the Chinese government’s weak position in its quasi-colonial relationship with the US – both politically and culturally – in terms of the appointment of architects, the design process, and the arrangement of construction. Such power interaction shaped an ambiguous ‘Chinese architecture’ presented at the fair, imitating the Beijing residence of a Chinese Prince while incorporating vernacular architectural elements from south China. It reflected the Chinese government’s early self-vision of its global image in an age of political turmoil and cultural uncertainty, and pioneered the exploration of an architectural ‘Chinese-ness’ in the early twentieth century.
Metrical evidence for the evolution of English syntax
Authors: RUSSOM GEOFFREY
Published: July 2022

Kuhn (1933) proposed that the evolution of Germanic syntax began with a need to restore acceptable sentence rhythm after a shift to fixed initial stress. Kuhn found support for his hypothesis in ‘laws’ for word placement that applied in alliterative poetry but not in prose. Kuhn assumed that his laws were syntactic rules of Proto-Germanic maintained by conservative poets. Here I argue that Kuhn's Laws were rules of poetic meter that obscured basic word order. Adopting the universalist approach in Russom (2017), I integrate Kuhn's Laws with the metrical constraints observed by Sievers (1893) and explore the interaction between meter and syntax. When there are no adverse metrical consequences, subject-object-verb order is employed with remarkable consistency inBeowulf, our most valuable source of poetic evidence. My analysis receives independent support from Smith (1971), a study of the earliest Germanic texts that focuses primarily on prose.
Effect of cotton herbicide programs on weed population trajectories and frequency of glyphosate-resistant Palmer amaranth (Amaranthus palmeri)
Authors: Oreja Fernando H. , Inman Matthew D. , Jordan David L. , Vann Matthew , Jennings Katherine M. , Leon Ramon G.
Published: July 2022

The adoption of dicamba-resistant cotton (Gossypium hirsutum L.) cultivars allows using dicamba to reduce weed populations across growing seasons. However, the overuse of this tool risks selecting new herbicide-resistant biotypes. The objectives of this research were to determine the population trajectories of several weed species and track the frequency of glyphosate-resistant (GR) Palmer amaranth (Amaranthus palmeri S. Watson) over 8 yr in dicamba-resistant cotton. An experiment was established in North Carolina in 2011, and during the first 4 yr, different herbicide programs were applied. These programs included postemergence applications of glyphosate, alone or with dicamba, with or without residual herbicides. During the last 4 yr, all programs received glyphosate plus dicamba. Biennial rotations of postemergence applications of glyphosate only and glyphosate plus dicamba postemergence with and without preemergence herbicides were also included. Sequential applications of glyphosate plus dicamba were applied to the entire test area for the final 4 yr of the study. No herbicide program was entirely successful in controlling the weed community. Weed population trajectories were different according to species and herbicide program, creating all possible outcomes; some increased, others decreased, and others remained stable. Density of resistant A. palmeri increased during the first 4 yr with glyphosate-only programs (up to 11,739 plants m−2) and decreased a 96% during the final 4 yr, when glyphosate plus dicamba was implemented. This species had a strong influence on population levels of other weed species in the community. Goosegrass [Eleusine indica (L.) Gaertn.] was not affected by A. palmeri population levels and even increased its density in some herbicide programs, indicating that not only herbicide resistance but also reproductive rates and competitive dynamics are critical for determining weed population trajectories under intensive herbicide-based control programs. Frequency of glyphosate resistance reached a maximum of 62% after 4 yr, and those levels were maintained until the end of the experiment.
Antikörpermangelsyndrome
Authors: Jandus Peter , Bitzenhofer-Grüber Michaela
Published: July 2022

Zusammenfassung. Die Primären Immundefekte (PID) werden durch eine genetisch bedingte Fehlentwicklung/Funktionsstörung des Immunsystems verursacht. Leitsymptome sind neben Infektanfälligkeit, Autoimmunerkrankungen, lymphoproliferative, allergische als auch malige Erkrankungen. Sie können in zehn Hauptgruppen unterteilt werden, worunter die primären Antikörpermangelsyndrome (PAD) bei den Erwachsenen dominieren. Zu den bekanntesten PAD gehören das variable Immundefektsyndrom (CVID), die Brutonsche Agammaglobulinämie, die IgG-Subklassendefekte, der Immunglobulin-A-Mangel, der spezifische Antikörpermangel und die transiente Hypogammaglobulinämie im Kindesalter. Sekundäre bedingte Hypogammaglobulinämien durch Medikamente, hämatologische Erkrankungen, Malignome und Infektionen sollten ausgeschlossen werden. Bei Diagnoseverzögerungen der CVID konnte eine signifikante Erhöhung der Morbidität und Zunahme der Mortalität nachgewiesen werden. Therapeutisch erfolgt neben Impfungen auch eine Immunglobulin-Ersatztherapie.
Einsamkeit bei Jugendlichen vor dem Hintergrund der COVID-19-Pandemie: Ein Risikofaktor
Authors: Hillert Sophia , Naab Silke , Hillert Andreas
Published: July 2022

Zusammenfassung. Einsamkeit, das subjektiver Erleben unzureichender sozialer Einbindung und Unterstützung, ist einerseits ein normales, im Rahmen individueller Entwicklung emotional und handlungsorientiert zu bewältigendes Phänomen. Andererseits gehen chronifizierte Einsamkeitskonstellationen mit erheblichem Leiden, reduzierter Lebensqualität und erhöhtem Risiko für psychische wie somatische Erkrankungen einher. Im Rahmen der aktuellen gesellschaftlichen, mit zunehmender Individualisierung einhergehenden Entwicklungen wurde eine Zunahme der Einsamkeitsproblematik von Jugendlichen berichtet. Einsamkeitserlebenreduzierende Interventionen sind dann wirksam, wenn sie, über soziale Angebote hinaus, auf die bei chronifizierter Einsamkeit häufige Dynamik (geringer Selbstwert, Bewertung neutraler Kommunikation als abwertend) fokussieren. Hinweise darauf, dass die Nutzung virtueller sozialer Netzwerke anhaltend das Einsamkeitserleben bei Jugendlichen reduziert, gibt es nicht. Darüber hinaus stellt sich die Frage, auf welcher Grundlage gemeinsamer Werte und Ziele soziale Integration sich einsam erlebender Jugendlicher perspektivisch möglich sein wird. Entsprechend den Ergebnissen erster systematischer Erhebungen zu den psychosozialen Folgen der COVID-19-Pandemie muss davon ausgegangen werden, dass die Einsamkeitsproblematik Jugendlicher durch die damit einhergehenden massiven Einschränkungen des realen sozialen Lebens weiter an Relevanz gewinnen wird.
TOB is an effector of the hippocampus-mediated acute stress response
Authors: Youssef Mohieldin M. M. , Hamada Hiro Taiyo , Lai Esther Suk King , Kiyama Yuji , El-Tabbal Mohamed , Kiyonari Hiroshi , Nakano Kohei , Kuhn Bernd , Yamamoto Tadashi
Published: July 2022

Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in psychological stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed changes in factors involved in stress response like decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study introduces TOB as an important modulator in the hippocampal stress signaling machinery. In summary, we reveal a molecular pathway and neural circuit mechanism by which Tob deletion contributes to expression of pathological stress-related behavior.
Lactate promotes metastasis of normoxic colorectal cancer stem cells through PGC-1α-mediated oxidative phosphorylation
Authors: Liu Shuang , Zhao Hui , Hu Yibing , Yan Chang , Mi Yulong , Li Xiaolan , Tao Deding , Qin Jichao
Published: July 2022

Uneven oxygen supply in solid tumors leads to hypoxic and normoxic regions. Hypoxic cells exhibit increased secretion of lactate, which creates an acidic tumor microenvironment (TME). This acidic TME is positively associated with tumor metastasis. Despite the increased metastatic capacity of hypoxic cells, they are located relatively further away from the blood vessels and have limited access to the circulatory system. Studies have shown that cancer stem cells (CSCs) are enriched for tumor metastasis-initiating cells and generally undergo aerobic respiration, which could be enhanced by lactate. We therefore hypothesized that TME-derived lactate may promote the metastasis of normoxic CSCs. In the present study, the abundance of hypoxic and normoxic CSCs was analyzed in primary CRC tumors. It was found that the proportion of normoxic CSCs was positively associated with tumor stage. Using two human CRC cell lines, LoVo and SW480, and a patient-derived xenograft (XhCRC), it was found that treatment with lactate promoted normoxic CSC metastasis. Metabolism analysis indicated that, upon treatment with lactate, oxidative phosphorylation (OXPHOS) activity in normoxic CSCs was enhanced, whereas hypoxic CSCs were rarely altered. At the molecular level, the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of lactate oxidation, was found to be elevated in normoxic CSCs. Furthermore, PGC-1α knockdown markedly reduced the metastatic potential of normoxic CSCs. Notably, both the PGC-1α-mediated OXPHOS activity and metastatic potential were impaired when hypoxia-inducible factor-1α (HIF-1α) was activated in normoxic CSCs. Together, these findings provide a therapeutic strategy against tumor metastasis through the targeting of PGC-1α and, thus, the suppression of lactate-feeding OXPHOS in normoxic CSCs may improve the therapeutic benefit of patients with cancer, particularly CRC.
Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression
Authors: Larivière Sara , Royer Jessica , Rodríguez-Cruces Raúl , Paquola Casey , Caligiuri Maria Eugenia , Gambardella Antonio , Concha Luis , Keller Simon S. , Cendes Fernando , Yasuda Clarissa L. , Bonilha Leonardo , Gleichgerrcht Ezequiel , Focke Niels K. , Domin Martin , von Podewills Felix , Langner Soenke , Rummel Christian , Wiest Roland , Martin Pascal , Kotikalapudi Raviteja , O’Brien Terence J. , Sinclair Benjamin , Vivash Lucy , Desmond Patricia M. , Lui Elaine , Vaudano Anna Elisabetta , Meletti Stefano , Tondelli Manuela , Alhusaini Saud , Doherty Colin P. , Cavalleri Gianpiero L. , Delanty Norman , Kälviäinen Reetta , Jackson Graeme D. , Kowalczyk Magdalena , Mascalchi Mario , Semmelroch Mira , Thomas Rhys H. , Soltanian-Zadeh Hamid , Davoodi-Bojd Esmaeil , Zhang Junsong , Winston Gavin P. , Griffin Aoife , Singh Aditi , Tiwari Vijay K. , Kreilkamp Barbara A. K. , Lenge Matteo , Guerrini Renzo , Hamandi Khalid , Foley Sonya , Rüber Theodor , Weber Bernd , Depondt Chantal , Absil Julie , Carr Sarah J. A. , Abela Eugenio , Richardson Mark P. , Devinsky Orrin , Severino Mariasavina , Striano Pasquale , Tortora Domenico , Kaestner Erik , Hatton Sean N. , Vos Sjoerd B. , Caciagli Lorenzo , Duncan John S. , Whelan Christopher D. , Thompson Paul M. , Sisodiya Sanjay M. , Bernasconi Andrea , Labate Angelo , McDonald Carrie R. , Bernasconi Neda , Bernhardt Boris C.
Published: July 2022

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.
Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity
Authors: Deaton Aimee M. , Dubey Aditi , Ward Lucas D. , Dornbos Peter , Flannick Jason ,   AMP-T2D-GENES Consortium, Yee Elaine , Ticau Simina , Noetzli Leila , Parker Margaret M. , Hoffing Rachel A. , Willis Carissa , Plekan Mollie E. , Holleman Aaron M. , Hinkle Gregory , Fitzgerald Kevin , Vaishnaw Akshay K. , Nioi Paul
Published: July 2022

Identifying genetic variants associated with lower waist-to-hip ratio can reveal new therapeutic targets for abdominal obesity. We use exome sequences from 362,679 individuals to identify genes associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI), a surrogate for abdominal fat that is causally linked to type 2 diabetes and coronary heart disease. Predicted loss of function (pLOF) variants inINHBEassociate with lower WHRadjBMI and this association replicates in data from AMP-T2D-GENES.INHBEencodes a secreted protein, the hepatokine activin E. In vitro characterization of the most commonINHBEpLOF variant in our study, indicates an in-frame deletion resulting in a 90% reduction in secreted protein levels. We detect associations with lower WHRadjBMI for variants inACVR1C, encoding an activin receptor, further highlighting the involvement of activins in regulating fat distribution. These findings highlight activin E as a potential therapeutic target for abdominal obesity, a phenotype linked to cardiometabolic disease.
Body size, shape and ecology in tetrapods
Authors: Maher Alice E. , Burin Gustavo , Cox Philip G. , Maddox Thomas W. , Maidment Susannah C. R. , Cooper Natalie , Schachner Emma R. , Bates Karl T.
Published: July 2022

Body size and shape play fundamental roles in organismal function and it is expected that animals may possess body proportions that are well-suited to their ecological niche. Tetrapods exhibit a diverse array of body shapes, but to date this diversity in body proportions and its relationship to ecology have not been systematically quantified. Using whole-body skeletal models of 410 extinct and extant tetrapods, we show that allometric relationships vary across individual body segments thereby yielding changes in overall body shape as size increases. However, we also find statistical support for quadratic relationships indicative of differential scaling in small-medium versus large animals. Comparisons of locomotor and dietary groups highlight key differences in body proportions that may mechanistically underlie occupation of major ecological niches. Our results emphasise the pivotal role of body proportions in the broad-scale ecological diversity of tetrapods.
Development of quasi-solid-state anode-free high-energy lithium sulfide-based batteries
Authors: Liu Yuzhao , Meng Xiangyu , Wang Zhiyu , Qiu Jieshan
Published: July 2022

Anode-free lithium batteries without lithium metal excess are a practical option to maximize the energy content beyond the conventional design of Li-ion and Li metal batteries. However, their performance and reliability are still limited by using low-capacity oxygen-releasing intercalation cathodes and flammable liquid electrolytes. Herein, we propose quasi-solid-state anode-free batteries containing lithium sulfide-based cathodes and non-flammable polymeric gel electrolytes. Such batteries exhibit an energy density of 1323 Wh L−1 at the pouch cell level. Moreover, the lithium sulfide-based anode-free cell chemistry endows intrinsic safety thanks to a lack of uncontrolled exothermic reactions of reactive oxygen and excess Li inventory. Furthermore, the non-flammable gel electrolyte, developed from MXene-doped fluorinated polymer, inhibits polysulfide shuttling, hinders Li dendrite formation and further secures cell safety. Finally, we demonstrate the improved cell safety against mechanical, electrical and thermal abuses.
Ammonia for post-healing of formamidinium-based Perovskite films
Authors: Li Zhipeng , Wang Xiao , Wang Zaiwei , Shao Zhipeng , Hao Lianzheng , Rao Yi , Chen Chen , Liu Dachang , Zhao Qiangqiang , Sun Xiuhong , Gao Caiyun , Zhang Bingqian , Wang Xianzhao , Wang Li , Cui Guanglei , Pang Shuping
Published: July 2022

Solvents employed for perovskite film fabrication not only play important roles in dissolving the precursors but also participate in crystallization process. High boiling point aprotic solvents with O-donor ligands have been extensively studied, but the formation of a highly uniform halide perovskite film still requires the participation of additives or an additional step to accelerate the nucleation rate. The volatile aliphatic methylamine with both coordinating ligands and hydrogen protons as solvent or post-healing gas facilitates the process of methylamine-based perovskite films with high crystallinity, few defects, and easy large-scale fabrication as well. However, the attempt in formamidinium-containing perovskites is challenged heretofore. Here, we reveal that the degradation of formamidinium-containing perovskites in aliphatic amines environment results from the transimination reaction of formamidinium cation and aliphatic amines along with the formation of ammonia. Based on this mechanism, ammonia is selected as a post-healing gas for a highly uniform, compact formamidinium-based perovskite films. In particular, low temperature is proved to be crucial to enable formamidinium-based perovskite materials to absorb enough ammonia molecules and form a liquid intermediate state which is the key to eliminating voids in raw films. As a result, the champion perovskite solar cell based on ammonia post-healing achieves a power conversion efficiency of 23.21% with excellent reproducibility. Especially the module power conversion efficiency with 14 cm2 active area is over 20%. This ammonia post-healing treatment potentially makes it easier to upscale fabrication of highly efficient formamidinium-based devices.
Metagenomic analysis reveals associations between salivary microbiota and body composition in early childhood
Authors: Coker Modupe O. , Lebeaux Rebecca M. , Hoen Anne G. , Moroishi Yuka , Gilbert-Diamond Diane , Dade Erika F. , Palys Thomas J. , Madan Juliette C. , Karagas Margaret R.
Published: July 2022

Several studies have shown that body mass index is strongly associated with differences in gut microbiota, but the relationship between body weight and oral microbiota is less clear especially in young children. We aimed to evaluate if there is an association between child growth and the saliva microbiome. We hypothesized that associations between growth and the saliva microbiome would be moderate, similarly to the association between growth and the gut microbiome. For 236 toddlers participating in the New Hampshire Birth Cohort Study, we characterized the association between multiple longitudinal anthropometric measures of body height, body weight and body mass. Body Mass Index (BMI) z-scores were calculated, and dual-energy x-ray absorptiometry (DXA) was used to estimate body composition. Shotgun metagenomic sequencing of saliva samples was performed to taxonomically and functionally profile the oral microbiome. We found that within-sample diversity was inversely related to body mass measurements while community composition was not associated. Although the magnitude of associations were small, some taxa were consistently associated with growth and modified by sex. Certain taxa were associated with decreased weight or growth (including Actinomyces odontolyticus and Prevotella melaninogenica) or increased growth (such as Streptococcus mitis and Corynebacterium matruchotii) across anthropometric measures. Further exploration of the functional significance of this relationship will enhance our understanding of the intersection between weight gain, microbiota, and energy metabolism and the potential role of these relationships on the onset of obesity-associated diseases in later life.
Genetic variation as a long-distance modulator of RAD21 expression in humans
Authors: Schierding William , Horsfield Julia A. , O’Sullivan Justin
Published: July 2022

Somatic mutations and changes in expression of RAD21 are common in many types of cancer. Moreover, sub-optimal levels of RAD21 expression in early development can result in cohesinopathies. Altered RAD21 levels can result directly from mutations in the RAD21 gene. However, whether DNA variants outside of the RAD21 gene could control its expression and thereby contribute to cancer and developmental disease is unknown. In this study, we searched for genomic variants that modify RAD21expression to determine their potential to contribute to development or cancer by RAD21 dysregulation. We searched 42,953,834 genomic variants for a spatial-eQTL association with the transcription of RAD21. We identified 123 significant associations (FDR < 0.05), which are local (cis) or long-distance (trans) regulators of RAD21 expression. The 123 variants co-regulate a further seven genes (AARD, AKAP11, GRID1, KCNIP4, RCN1, TRIOBP, and USP32), enriched for having Sp2 transcription factor binding sites in their promoter regions. The Sp2 transcription factor and six of the seven genes had previously been associated with cancer onset, progression, and metastasis. Our results suggest that genome-wide variation in non-coding regions impacts on RAD21 transcript levels in addition to other genes, which then could impact on oncogenesis and the process of ubiquitination. This identification of distant co-regulation of oncogenes represents a strategy for discovery of novel genetic regions influencing cancer onset and a potential for diagnostics.
A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2
Authors: Kashyap Prakriti , Bhardwaj Vijay Kumar , Chauhan Mahima , Chauhan Varun , Kumar Asheesh , Purohit Rituraj , Kumar Arun , Kumar Sanjay
Published: July 2022

COVID-19 pandemic caused by SARS-CoV-2 led to the research aiming to find the inhibitors of this virus. Towards this world problem, an attempt was made to identify SARS-CoV-2 main protease (Mpro) inhibitory peptides from ricin domains. The ricin-based peptide from barley (BRIP) was able to inhibit Mpro in vitro with an IC50 of 0.52 nM. Its low and no cytotoxicity upto 50 µM suggested its therapeutic potential against SARS-CoV-2. The most favorable binding site on Mpro was identified by molecular docking and steered molecular dynamics (MD) simulations. The Mpro-BRIP interactions were further investigated by evaluating the trajectories for microsecond timescale MD simulations. The structural parameters of Mpro-BRIP complex were stable, and the presence of oppositely charged surfaces on the binding interface of BRIP and Mpro complex further contributed to the overall stability of the protein-peptide complex. Among the components of thermodynamic binding free energy, Van der Waals and electrostatic contributions were most favorable for complex formation. Our findings provide novel insight into the area of inhibitor development against COVID-19.