Learning from Retracted Papers Authored by the Highly Cited Iran-affiliated Researchers: Revisiting Research Policies and a Key Message to Clarivate Analytics.

Reasons underlying retractions of papers authored by the Iran-affiliated highly cited researchers (HCRs) have not been documented. Here, we report that 229 of the Iran-affiliated researchers were listed by the Clarivate Analytics as HCRs. We investigated the Retraction Watch Database and found that, in total, 51 papers authored by the Iran-affiliated HCRs were retracted from 2006 to 2019. Twenty-three of the 229 HCRs (10%) had at least one paper retracted. One of the listed HCRs had 22 papers retracted; 14 of the 23 (60.8%) had only one paper retracted. Among the 51 retracted papers, three had been authored by two female authors. Eight (16.8%) retracted papers had international co-authorships. The shortest and longest times from publication to retraction were 20 and 2610 (mean ± SD, 857 ± 616) days, respectively. Of the 51 papers, 43 (84%) had a single reason for retraction, whereas eight had multiple reasons. Among the 43 papers, 23 (53%) were retracted due to fake peer-review, eight (19%) were duplications, six (14%) had errors, four (9%) had plagiarism, and two (5%) were labelled as "limited or no information." Duplication of data, which is easily preventable, amounted to 27%. Any publishing oversight committed by an HCR may not be tolerated because they represent the stakeholders of the scientific literature and stand as role-models for other peer researchers. Future policies supporting the Iranian academia should radically change by implementation of educational and awareness programs on publishing ethics to reduce the rate of retractions in Iran.

Ablation of the ASCT2 (SLC1A5) gene encoding a neutral amino acid transporter reveals transporter plasticity and redundancy in cancer cells.

The neutral amino acid transporter solute carrier family 1 member 5 (SLC1A5 or ASCT2) is overexpressed in many cancers. To identify its roles in tumors, we employed 143B osteosarcoma cells and HCC1806 triple-negative breast cancer cells with or without ASCT2 deletion. ASCT2ko 143B cells grew well in standard culture media, but ASCT2 was required for optimal growth at <0.5 mm glutamine, with tumor spheroid growth and monolayer migration of 143B ASCT2ko cells being strongly impaired at lower glutamine concentrations. However, the ASCT2 deletion did not affect matrix-dependent invasion. ASCT2ko 143B xenografts in nude mice exhibited a slower onset of growth and a higher number of small tumors than ASCT2wt 143B xenografts, but did not differ in average tumor size 25 days after xenotransplantation. ASCT2 deficiency was compensated by increased levels of sodium neutral amino acid transporter 1 (SNAT1 or SLC38A1) and SNAT2 (SLC38A2) in ASCT2ko 143B cells, mediated by a GCN2 EIF2α kinase (GCN2)-dependent pathway, but this compensation was not observed in ASCT2ko HCC1806 cells. Combined SNAT1 silencing and GCN2 inhibition significantly inhibited growth of ASCT2ko HCC1806 cells, but not of ASCT2ko 143B cells. Similarly, pharmacological inhibition of l-type amino acid transporter 1 (LAT1) and GCN2 significantly inhibited growth of ASCT2ko HCC1806 cells, but not of ASCT2ko 143B cells. We conclude that cancer cells with reduced transporter plasticity are more vulnerable to disruption of amino acid homeostasis than cells with a full capacity to up-regulate redundant transporters by an integrated stress response.

Characterization of the ATP4 ion pump in Toxoplasma gondii.

The Plasmodium falciparum ATPase PfATP4 is the target of a diverse range of antimalarial compounds, including the clinical drug candidate cipargamin. PfATP4 was originally annotated as a Ca2+ transporter, but recent evidence suggests that it is a Na+ efflux pump, extruding Na+ in exchange for H+ Here we demonstrate that ATP4 proteins belong to a clade of P-type ATPases that are restricted to apicomplexans and their closest relatives. We employed a variety of genetic and physiological approaches to investigate the ATP4 protein of the apicomplexan Toxoplasma gondii, TgATP4. We show that TgATP4 is a plasma membrane protein. Knockdown of TgATP4 had no effect on resting pH or Ca2+ but rendered parasites unable to regulate their cytosolic Na+ concentration ([Na+]cyt). PfATP4 inhibitors caused an increase in [Na+]cyt and a cytosolic alkalinization in WT but not TgATP4 knockdown parasites. Parasites in which TgATP4 was knocked down or disrupted exhibited a growth defect, attributable to reduced viability of extracellular parasites. Parasites in which TgATP4 had been disrupted showed reduced virulence in mice. These results provide evidence for ATP4 proteins playing a key conserved role in Na+ regulation in apicomplexan parasites.

Criticality of physical/social distancing, handwashing, respiratory hygiene and face-masking during the COVID-19 pandemic and beyond.

Physical/social distancing, handwashing, respiratory hygiene and face-masking have been recommended as realistic counterstrategies to control the COVID-19 pandemic. These strategies have been critical in the fight against the present pandemic in many countries. Here we detail the background to such countermeasures, present some examples in different settings and finally emphasise that they should remain in place worldwide as a cultural and behavioural "new normal" until a vaccine or a decisive treatment for COVID-19 is developed and made available globally.

Plagiarism, Fake Peer-Review, and Duplication: Predominant Reasons Underlying Retractions of Iran-Affiliated Scientific Papers.

Retractions of scientific papers published by some Iran-affiliated scientists in the preceding decade have attracted much attention and publicity; however, the reasons for these retractions have not been documented. We searched the Retraction Watch Database to enumerate the retracted Iran-affiliated papers from December 2001 to December 2019 and aimed to outline the predominant reasons for retractions. The reasons included fake peer-review, authorship dispute, fabricated data, plagiarism, conflict of interest, erroneous data, and duplication. The Fisher's exact test was used to investigate the associations between retractions and their underlying reasons. We selected P < 0.05 to indicate the statistically significant differences. We found 697 retracted papers. Duplication (27%), plagiarism (26%), and fake peer-review (21%) were the most frequent reasons for retractions. Our study highlights the importance of urgent intervention to prevent the misconduct and questionable research practices that lead to retractions in Iran. Continually educating the scientists and postgraduate students about the ethics and norms of scientific publishing is an important measure to ensure publication of reliable, worthy, and impactful papers.

Aptamers Selected for Recognizing Amyloid ß-Protein-A Case for Cautious Optimism.

Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid ß-protein (Aß) has been limited so far. Aß is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of Aß, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different Aß assemblies likely due to the metastable nature of Aß or inherent affinity of RNA oligonucleotides to ß-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from Aß-aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers' specificity are important for realizing and garnering the full potential of aptamers selected for recognizing Aß or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different Aß assemblies and highlights controversies, difficulties, and limitations of such studies.

Deletion of Amino Acid Transporter ASCT2 (SLC1A5) Reveals an Essential Role for Transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to Sustain Glutaminolysis in Cancer Cells.

Many cancer cells depend on glutamine as they use the glutaminolysis pathway to generate building blocks and energy for anabolic purposes. As a result, glutamine transporters are essential for cancer growth and are potential targets for cancer chemotherapy with ASCT2 (SLC1A5) being investigated most intensively. Here we show that HeLa epithelial cervical cancer cells and 143B osteosarcoma cells express a set of glutamine transporters including SNAT1 (SLC38A1), SNAT2 (SLC38A2), SNAT4 (SLC38A4), LAT1 (SLC7A5), and ASCT2 (SLC1A5). Net glutamine uptake did not depend on ASCT2 but required expression of SNAT1 and SNAT2. Deletion of ASCT2 did not reduce cell growth but caused an amino acid starvation response and up-regulation of SNAT1 to replace ASCT2 functionally. Silencing of GCN2 in the ASCT2(-/-) background reduced cell growth, showing that a combined targeted approach would inhibit growth of glutamine-dependent cancer cells.

ChatGPT and Corporations of Mega-journals Jeopardize the Norms That Underpin Academic Publishing.

Those who participate in and contribute to academic publishing are affected by its evolution. Funding bodies, academic institutions, researchers and peer-reviewers, junior scholars, freelance language editors, language-editing services, and journal editors are to enforce and uphold the ethical norms on which academic publishing is founded. Deviating from such norms will challenge and threaten the scholarly reputation, academic careers, and institutional standing; reduce the publishers' true impacts; squander public funding; and erode the public trust to the academic enterprise. Rigorous review is paramount because peer-review norms guarantee that scientific findings are scrutinized before being publicized. Volunteer peer-reviewers and guest journal editors devote an immense amount of unremunerated time to reviewing papers, voluntarily serving the scientific community, and benefiting the publishers. Some mega-journals are motivated to mass-produce publications and attract the funded projects instead of maintaining the scientific rigor. The rapid development of mega-journals may diminish some traditional journals by outcompeting their impacts. Artificial intelligence (AI) tools/algorithms such as ChatGPT may be misused to contribute to the mass-production of publications which may have not been rigorously revised or peer-reviewed. Maintaining norms that guarantee scientific rigor and academic integrity enable the academic community to overcome the new challenges such as mega-journals and AI tools.

Zn2+-Aß40 complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons.

The roles of metal ions in promoting amyloid ß-protein (Aß) oligomerization associated with Alzheimer disease are increasingly recognized. However, the detailed structures dictating toxicity remain elusive for Aß oligomers stabilized by metal ions. Here, we show that small Zn(2+)-bound Aß1-40 (Zn(2+)-Aß40) oligomers formed in cell culture medium exhibit quasi-spherical structures similar to native amylospheroids isolated recently from Alzheimer disease patients. These quasi-spherical Zn(2+)-Aß40 oligomers irreversibly inhibit spontaneous neuronal activity and cause massive cell death in primary hippocampal neurons. Spectroscopic and x-ray diffraction structural analyses indicate that despite their non-fibrillar morphology, the metastable Zn(2+)-Aß40 oligomers are rich in ß-sheet and cross-ß structures. Thus, Zn(2+) promotes Aß40 neurotoxicity by structural organization mechanisms mediated by coordination chemistry.

Passive Contribution of ChatGPT to Scientific Papers.

Arguably ChatGPT jeopardizes the integrity and validity of the academic publications instead of ethically facilitating them. ChatGPT can apparently fulfill a portion of one of the four authorship criteria set by the International Committee of Medical Journal Editors (ICMJE), i.e., "drafting." However, the authorship criteria by ICMJE must all be collectively met, not singly or partially. Many published manuscripts or preprints have credited ChatGPT by including it in the author byline, and the academic publishing enterprise seems to be unguided on how to handle such manuscripts. Interestingly, PLoS Digital Health removed ChatGPT off a paper which had ChatGPT listed initially in the author byline of the preprint version. Revised publishing policies are, thus, promptly required to guide a consistent stance regarding ChatGPT or similar artificial content generators. Publishing policies must accord among publishers, preprint servers ( https://asapbio.org/preprint-servers ), universities, and research institutions worldwide and across different disciplines. Ideally, considering any declaration of the contribution of ChatGPT to writing any scientific article should be recognized as publishing misconduct immediately and be retracted. Meanwhile, all parties involved in the scientific reporting and publishing must be educated about how ChatGPT fails to meet the essential authorship criteria, so that no author must submit a manuscript with ChatGPT contributing as a "co-author." Meanwhile, using ChatGPT for writing laboratory reports or short summaries of experiments may be acceptable, but not for academic publishing or formal scientific reporting.

ChatGPT and Publication Ethics.

Academic publishing is crucial for scientific communication, is governed by accepted ethical norms, and underpins the collective literature on basic science, and technological and medical principles and advances. In November 2022, the public and professional global communities, including the scientific community, witnessed the release of ChatGPT by OpenAI in San Francisco, California, USA. Excluding its public appeal and entertaining aspects but considering its diverse potential applications, some ethical concerns must be considered before establishing guidelines on using and including ChatGPT or similar platforms in scientific publishing. Some academic publishers and preprints have accepted manuscripts with ChatGPT listed as a "co-author". Though excluding such platforms from scientific publishing may not be practicable with time, establishing ethical principles is essential before ChatGPT could become a "co-author" in any scientific, published manuscript.

Inhibition of GCN2 Reveals Synergy with Cell-Cycle Regulation and Proteostasis.

The integrated stress response is a signaling network comprising four branches, each sensing different cellular stressors, converging on the phosphorylation of eIF2α to downregulate global translation and initiate recovery. One of these branches includes GCN2, which senses cellular amino acid insufficiency and participates in maintaining amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is induced by inhibiting an additional target. In this light, we screened numerous drugs for their potential to synergize with the GCN2 inhibitor TAP20. The drug sensitivity of six cancer cell lines to a panel of 25 compounds was assessed. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was evaluated. The strongly synergistic combinations were further characterized using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis and the MEK-ERK pathway, as well as the pan-CDK inhibitors, flavopiridol, and seliciclib, were potently synergistic with TAP20 in two cell lines. Among their common CDK targets was CDK7, which was more selectively targeted by THZ-1 and synergized with TAP20. Moreover, these combinations were partially synergistic when assessed using matrix-dependent invasion assays. However, TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 inhibition can be further explored in vivo as a cancer target.

SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19.

The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed.

Is Omicron the last SARS-CoV-2 Variant of Concern?

Millions have died due to the COVID-19 pandemic. The irrepressible propensity of the pandemic, which was highlighted by the outbreak of the Delta variant, should not be underestimated. The Omicron SARS-CoV-2 variant is thought to have originated from Africa. Sequences of the omicron variant show that it carries the highest number of point mutations detected in a betacoronavirus. High hospitalization numbers due to the Omicron variant has retriggered precautionary restrictions and border closures even in countries which have attained herd immunity by mass vaccinations. Surveillance systems for accurate screening of the Omicron variant are needed to guide implementation of hygiene principles and restrictions. Development of vaccines against the variants is important as the pandemic evolves. Whether Omicron is the last variant depends on the success of the local and global public-health strategies against SARS-CoV-2.

Identification of Streptococcus gallolyticus in tumor samples of Iranian patients diagnosed with colorectal cancer.

OBJECTIVE: Clinical outcomes of infection by S. gallolyticus have not been investigated extensively. We aimed to determine the prevalence of S. gallolyticus in tumor specimens obtained from Iranian patients diagnosed with colorectal cancer. Polymerase chain reaction was used to confirm the presence of S. gallolyticus in patients' tissue samples. RESULTS: Of 176 patients, 65 were diagnosed with colorectal cancer whereas 111 did not have any colon disease. No correlation was found between age, colonization with S. gallolyticus, gender, or risk factors. Overall, 72 (40%) patients carried S. gallolyticus; only 29% of the patients without colorectal cancer were positive for S. gallolyticus. Diagnosis of colorectal cancer and presence of S. gallolyticus significantly correlated (P = 0.006; odds ratio = 1.46; 95% CI = 1.21-3.87). Among the patients with colorectal cancer, 39 (60%) were positive with S. gallolyticus (P = 0.006) whereas 33 of 111 (29.7%) control subjects were positive for S. gallolyticus (P > 0.05); thus, 70.3% of the control subjects were not infected with S. gallolyticus. We found a high prevalence of S. gallolyticus among an Iranian cohort of patients with colorectal cancer. Despite previous reports, we report a positive correlation between colorectal cancer and S. gallolyticus colonization.

Pleiotropic roles of S100A12 in coronary atherosclerotic plaque formation and rupture.

Macrophages, cytokines, and matrix metalloproteinases (MMP) play important roles in atherogenesis. The Ca(2+)-binding protein S100A12 regulates monocyte migration and may contribute to atherosclerosis by inducing proinflammatory cytokines in macrophages. We found significantly higher S100A12 levels in sera from patients with coronary artery disease than controls and levels correlated positively with C-reactive protein. S100A12 was released into the coronary circulation from ruptured plaque in acute coronary syndrome, and after mechanical disruption by percutaneous coronary intervention in stable coronary artery disease. In contrast to earlier studies, S100A12 did not stimulate proinflammatory cytokine production by human monocytes or macrophages. Similarly, no induction of MMP genes was found in macrophages stimulated with S100A12. Because S100A12 binds Zn(2+), we studied some functional aspects that could modulate atherogenesis. S100A12 formed a hexamer in the presence of Zn(2+); a novel Ab was generated that specifically recognized this complex. By chelating Zn(2+), S100A12 significantly inhibited MMP-2, MMP-9, and MMP-3, and the Zn(2+)-induced S100A12 complex colocalized with these in foam cells in human atheroma. S100A12 may represent a new marker of this disease and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive MMP-2 and MMP-9 activities by sequestering Zn(2+).

Alzheimer Disease: Controversies in Basic Science Research, Different Theories, and Reasons for Failed Trials.

Dementia comprises a collection of cognitive and sensory symptoms, including memory loss, communication difficulties, difficulty in planning and problem solving, disorientation and confusion, compromised olfaction, loss of visual perception, agnosia; and psychological symptoms, including personality and behavioral changes, depression, anxiety, hallucination, mood swings, agitation, and apathy [...].

SARS-CoV-2 Lambda (C.37): An emerging variant of concern?

Many SARS-CoV-2 variants have high infectivity and transmissibility. The viral genome data show that the COVID-19 curves of daily case numbers were shaped by the emergence of the variants, including Alpha 202012/01 GRY (B.1.1.7; the U.K.), Beta GH/501Y.V2 (B.1.351, B.1.351.2, and B.1.351.3; South Africa), Gamma GR/501Y.V3 (P.1, P.1.1, and P.1.2; Japan, Brazil), Eta G/484K.V3 (B.1.525; Nigeria, the U.K.), Delta G/478K.V1 (B.1.617.2, AY.1, AY.2, and AY.3; India), Iota GH/253G.V1 (B.1.526; the U.S.A.), and Kappa G/452R.V3 (B.1.617.1; India). The Lambda (C.37) variant was reported in Peru initially; this has spread to 41 countries in four continents. Seven out of eight mutations in this variant are associated with the viral spike protein, akin to mutations in the other variants. These mutations have implications for effectiveness of the vaccines and neutralizing antibodies in immunized subjects and those previously infected with the virus and are thought to facilitate the viral invasion into host cells and help the virus evade the host immune system. Widespread dissemination of the viral variants may cause severe clinical consequences, lengthy hospitalizations, and unfavorable prognoses. Healthcare systems will be stretched, and health workers will be fatigued. Fast, equitable, and widespread vaccination with strict adherence to hygiene protocols will control the rising curves of the pandemic due to the new variants.

Implications of the Emergence of a New Variant of SARS-CoV-2, VUI-202012/01.

Twelve months after the realization that SARS-CoV-2 caused a respiratory syndrome in Wuhan, China, with the constantly worsening COVID-19 pandemic and economic crisis globally, and with international news of vaccine development, a new viral variant, referred to as "SARS-CoV-2 VUI-202012/01" or "B.1.1.7" has been reported in London and southeast England. The variant may have emerged in late September 2020 and carries some 17 mutations. Whether a single or a combination of different mutations would change the viral transmissibility, virulence, clinical and epidemiological presentations, or vaccine efficiency is unknown. Transmission by asymptomatic carriers of the new variant is also unknown. Mutation pressure by antiviral agents or vaccines have not yet been induced; however, additional mutations are expected following global vaccination and, later, after administration of validated treatments. Thus, preparedness for fast emergence of new variants is prudent. One can also expect less virulent but highly transmissible variants, which could facilitate herd immunity. Development of clinical and rapid laboratory tests is required to follow up the vaccinated individuals for a secondary infection potentially by the new variant. Importantly, restrictive countermeasures, personal hygiene, face-masking, spatial distancing, and travel bans remain pertinent in fighting the virus.